chapter 8: Protein structure Flashcards
A polymer’s secondary structure is defines as what?
the local conformation of its backbone
Secondary structures include what?
- helices
- Pleated sheets
- Beta turns
A peptides C-N bond is 0.13 shorter than what?
its N-C alpha single bond The
When does a peptides bond have a maximum resonance energy?
~85 kJ * mol^-1 is maximum resonance energy. It occurs when the peptide group is planar because it pi bonding over lap is maximized in its conformation.
peptides with few exceptions assume what conformation?
Trans
How are Carbon alpha atoms orientated if peptide is in trans ?
Successive alpha carbons are on opposite sides of the peptide joining them
Why do peptides not typically take a cis configuration?
Steric interference causes Cis conformation to be less stable than trans conformation
what is an energy barrier of a peptide bond to rotate about the C-C single bond.
The energy difference between the staggered and eclipsed conformation
Substitutents other than hydrogen exhibit greater steric interference thus do what?
increase the size of energy barrier due to their greater bulk.
What do “forbidden” conformations arise from?
collision of successive amide groups.
When are “forbidden” conformations allowed?
If twist of only a few degrees about the peptide bond are permitted
Gly is the only residue with out what? menaing?
only carbon without s beta carbon thus it is less sterically hindered than the other amino acid residues
Gly often occupies positions where?
Where a polypeptide backbone makes a sharp turn which with any other residue would be subject to sterical hinderance
Helices are what structure?
Secondary
If a polypeptide chain is twisted by the same amount of each of its alpha carbons it assumes what conformation?
Helices
In a helical polypeptide chain what does n stand for?
Number of peptide units per helical turn
In a helical polypeptide chain what does p stand for?
pitch; the distance the helix rises along its axis per turn..
Does a helix have chirality?
Yes; can be left handed or right handed
There is only one helical polypeptide conformation that simultaneously allowed conformation angles and a favorable hydrogen bonding pattern. What is it?
Alpha helix
For polypeptides made from L alpha amino sugars what type of helix do they have
Right handed alpha helix with 3.6 residues per turn
The hydrogen bonds on alpha helix are arranged how?
The peptide N-H bond of the nth residue points along the helix towards the peptide C=O group of the (n-4)th residue.
Alpha helices have strong hydrogen bonds with nearly optimum distance of what?
of 2.8 A of N…O
How is the core of an alpha helix?
tightly packed so the atoms are in van der waals contact across the helix thus maximizing association energies
What is one reason why a left handed helix has never been observed?
Its helical parameters are mildly forbidden; its side chains contact its polypeptide back bone too closely.
Alpha helix is a common secondary structural unit of both___ and ____
globular proteins and fibrous proteins
In globular proteins an alpha helics on average spans _____ residues
~12 residues corresponding to over 3 helical turns
Beta pleated sheets is an example of what?
Secondary structure
How does hydrogen binding occure in Beta pleated sheets?
Hydrogen bonding occurs between neighboring polypeptide chains unlike alpha helices whose hydrogen bonding is within one
What are the two varieties of Beta pleated sheets?
1) parallel- hydrogen bonded chains extend in same direction
2) antiparallel- neighboring hydrogen bonded polypeptide chains run in opposite direction
In globular proteins Beta sheets consist of how many polypeptide strands?
2-22 polypepide strands with an average of 6 strands.
The polypepetide chains in a Beta sheet are known to be up to how long?
15 residues long with average being 6 residues
What is concanavalin A
jack bean proteins with a 7 strand antiparallel B sheet
parallel Beta sheets of less than how many sheets are rare? What does this indicate
less than 5 this indicates parallel beta sheets are less stable than antiparallel beta sheets.
What is one possibility in which antiparallel beta sheets are more stable than parallel beta sheets?
Because the hydrogen bonds of parallel sheets are distorted in comparison to the hydrogen bonds of antiparallel sheets
Mixed parallel-antiparallel sheets are common but what percent of the mx is typically parallel?
20% of the strand in Beta sheets have parallel bonding on one side and antiparallel bonding on the other vs an expected 50% for random mixing
What do beta sheets in globular proteins exhibit?
A right hand twist when viewed along their polypeptide strands
Beta sheets often form waht?
Central cores
Conformational energy calculations indicate that a Beta sheets right handed twist is a consequence of what?
nonbonded interactions between the chiral L amino acid residues in the sheet’s extended polypeptide chain;These interactions tend to give the polypeptide chains a slight right hand helical twist.
What effect does the slight right hand helical twist of Beta sheets have on its hydrogen bonding?
Distorts and weakens the Beta sheet’s interchain hydrogen bonds.
A particular Beta sheet geometry is the result of a compromise between what?
optimizing conformational energies of polypeptide chains and preserving its hydrogen bonds
How do you find change in H for a reaction such as peptide formation?
Sum (bond enthalpies products)- Sum(bond enthalpies reactants) which needs to be coupled witha favorable reaction such as ATP hydrolysis
Primary structure is what?
Protein sequence
Secondary structure is repetitive and non repetitive what?
structural elements like helices, Beta pleated sheets and Beta turns
Super-secondary structure or Motif is what?
common combinations of secondary structural elements such as hair pin
Tertiary structure or fold is what?
Is its 3 D arrangement; Combination of motifs (secondary structures) together with spatial dispositions of its side chains. An example of tertiary structure is Beta sandwich
Quaternary structure is what?
spatial arrangement between sub units
Domain is what?
Structurally independent units of large proteins that each have the characteristics of a small, globular protein.
Globular proteins consists of on average ~31% alpha helix and 28% Beta sheets the remaining polypeptide segments are
coil or loop conformation which are still secondary structures and no less ordered they are irregular so more difficult to describe.
Are coil and random coil the same thing?
No random coil means totaly disordered and rapidly fluctuating set of conformations assumed by denatured proteins and other polymers in solution
Globular proteins consists of largely of ~ straight runs of secondary structure joined by stretches of polypeptides that abruptly switch directions called
reverse turns or Beta turns
Beta turns often connect what type of successive strands?
antiparallel Beta sheets but can connect secondary structures in general
Beta turns almost always occur where?
protein surface
Most Beta/reverse turns involve how many amino cid residues?
4 successive amino acid residues
How are the successive amino acid residues or a Beta/reverse turn arranged?
In one of two ways:
Type I or Type II that differ by a 180 degree flip of the peptide unit linking residue 2 and 3.
Describe type I arrangement of Beta/reverse turns
Type I beta bends may be distorted sections of 3(10) helix
Describe type II arrangement of Beta/reverse turns?
The oxygen atom of residue 2 crowds the Beta carbon of residue 3 which is usually Glycine.
Why is the second residue of both type I and Type II beta turns usually pro?
since it can facilely assume the required conformation.
extended charged surface groups like Lys side chains are what?
examples of regions in proteins that are truly disordered
The N or C termini of polypeptide chains are examples of what?
Regions in proteins that are truly disordered
What functional roles may disordered regions in proteins have? What does this indicate?
binding to specific molecules. This indicates that the segment may be disordered in one state of the protein (molecule absent) but ordered in another state (molecule bond)
Keratin is what type of protein?
Fibrous protein
Keratin is found where?
In skin, nails, horns, and feathers
What type of keratin does mammals have?
alpha keratin
What type of keratin does birds and reptiles have?
Beta keratin
How many different types of alpha keratin genes does mammals have?
more than 50
What keratin types does the skin of mammals consist of?
Type I- acidic polypeptides
and Type II- basic polypeptides
What alpha keratin types does the skin of mammals consist of?
Type I- acidic polypeptides
and Type II- basic polypeptides
Type 3 collagen is most commonly found where?
In the blood vessels and fetal skin
Type 2 collagen is most commonly found where?
cartilage and invertebrate disks
Type I alpha collagen is most commonly found where?
- skin
- bone
- tendon
- blood vessels
- cornea
What is the most abundant type of protein in vertebrates?
Collagen
How many types of collagen is there?
26 differnt types
How many different gene products that associate as 3 polypeptide chains of collagen is there?
46
Four separate chains of hemoglobin assembled into an oligomeric protein is what type of structure?
Quaternary
One complete protein chain such as a beta chain of hemoglobin is an example of what structure?
Tertiary structure
Hair pin connection between antiparallel Beta strands is what?
In the plane of the sheet
myoglobin consist of only what?
alpha helices spanned by short connecting links that have coil conformations
Concanavalin A have _____ but lack ____
have Beta sheets but lack alpha helices
The primary structure of globular proteins lack what that are responsible for regular conformations of fibrous proteins
lacking repeating or pseudorepeating sequences
The amino acid side chains in globular proteins are spatially distributed how?
Based on polarity
Where are the nonpolar side chains of a globular protein located?
in interior of protein, out of contact with aqueous solution
How does the location of the nonpolar side chains contribute to protein’s 3D structure?
Hydrophobic interactions promote this distribution and thus largely responsible for 3D structure of native proteins
Where are the uncharged polar side chains of globular proteins located?
Typically on protein surface but frequently also occur in the interior of the molecule.
Where are the charged polar side chains of globular proteins located?
Largely located on the surface of a protein in contact with the aqueous solvent.
Why are charged polar side chains of globular proteins located where they are?
located on surface in contact with aqueous solvent because the immersion of an ion in the virtually anhydrous interior of a protein results in the uncompensatable lossof much of its hydration energy.
What roles may the few charged polar side chains of globular proteins located in the interior play?
specific chemical functions such as promoting catalysis or participating in metal ion binding.
If uncharged polar groups of globular proteins occur in the interior of the molecule are almost always what?
almost always hydrogen bonded to other groups of proteins; nearly all buried hydrogen bond donors form hydrogen bonds buried acceptor groups
How do uncharged polar groups of globular proteins that occur in the interior of the molecule “neutralize” the polarity?
Hydrogen bonding of buried hydrogen bond donor to buried hydrogen bond acceptor neutralizes polarity of hydrogen bonding group
Globular proteins are tightly packed therefore there is little ____
space inside them thus water is excluded from the interiors
Polypeptides that consist of more than ~ 200 residues usually fold how?
into two or more globular clusters known as domains which often gives these proteins a bi- or multilobal appearance.
Most domains consist of what?
100 -200 amino acid residues.
Domains are structurally independent units that each have characteristics of what?
of a small globular protein
A polypeptide chain usually wanders back and forth within a domain and are usually connected how?
by one or less commonly two polypeptide segments
Beta-Alpha-Beta motif is what type of structure?
Super secondary Structure
Beta hairpin motif is what type of structure?
Super secondary structure
The alpha alpha motif is what type of structure?
Super Secondary Structure
What is the most common form of super secondary structure?
Beta alpha Beta motif
The Greek key motif is what type of structure?
Super Secondary Structure
What is the Beta alpha Beta motif?
right handed crossover connection between two consecutive parallel strands of a Beta sheet consisting of an alpha helix.
What is the Beta hairpin motif?
consist of antiparallel Beta sheet formed by sequential segments of polypeptide chain that are connected by relitively tight reverse turns.
What is alpha alpha motif?
two successive antiparallel alpha helices pack against each other with their axes inclined so as to permit their contracting side chains to interdigitate efficiently.
The alpha alpha motif is energetically favorable associations stabilize the coiled coil conformation of what?
alpha keratin
What is the Greek key Motif
A Beta hairpin is folded over to form a four-stranded antiparallel Beta sheet.
Groups of motifs form together to form tertiary structure of a domain called a
fold
half of proteins known structure belong to only how many fold groups?
20
What is the simplest way to name domain (tertiary) structures?
as:
- alpha domains (secondary structural elements exclusively alpha helices)
- Beta domains
- and alpha/beta domains
the alpha/beta domain may be further divided into what two categories?
1) alpha/beta barrels
2) Open Beta sheets
Globin fold
- fold containing only alpha helices
- contains 8 helices in two layers
- occurs in myoglobin
- occurs in both the alpha and Beta chains of hemoglobin
4-helix bundle
- tertiary structure
- all alpha fold
- occurs in cytochrome b526.
- side chains in this fold highly hydrophobic
- sidechains intermesh and are out of contact with surrounding aqueous solution.
- Not all have up-down-up-down topology (connectivity) of cytochrome b562.
Human growth hormone
- tertiary structure is 4- helix bundle (thus all alpha fold)
- up-up-down-down topology.
- successive parrallel helices in fold are joined by longer loops than helicies joined in antiparallel.
4 helix bundle is what type of fold
all alpha helix
Beta sandwich is an example of what?
Tertiary strucuter; pure Beta domain
Beta domain contain what strands? arranged how?
4 to >10 predominately antiparallel Beta strands arranged in two sheets that pack against each other to form a Beta sandwich.
Immunoglobulin fold is an example of what?
Beta domain
In Beta sandwich the two sheets that pack against each other are what?
not parallel to one another, a characteristic of stacked Beta sheets.
The side chains between two stacked Beta sheets are what?
out of contact with aqueous medium thus form the domain’s core.
Since successive residues in a Beta strand alternatively extend to opposite sides of the Beta sheet these resdiues are what?
alternatively hydrophobic and hydrophilic
The inherent curvature of Beta sheets of more than 6 strands tend to cause what?
cause them to roll up into Beta barrels.
Beta Sandwich can be considered what in terms of Betta barrels?
flattened Beta barrels.
Up and down Beta barrel
- type of Beta domain
- consist of 8 successive antiparallel Beta strands arranged like staves of a barrel.
Retinol binding protein is an example of what?
Beta barrel which is has a tertiary structure of Beta domain
A fold consisting of 2 Greek key motifs is what?
- Beta barrel which is tertiary Beta Domain
- connects 8 strands in antiparallel Beta barrel
Jelly or swiss Roll Barrel
- Beta barrel which is the tertiary structure Beta domain
- 4 segment Beta hairpin is rolled up into 8 stranded antiparallel Beta barrel
Triose phosphate isomerase is also called what
TIM
TIM is what type of Domain
alpha/beta barrel
In alpha beta domains what occurs?
A central parallel or mixed Beta sheet is flanked by alpha helices
eight overlapping Beta alpha Beta motifs is an example of what?
alpha/beta barrel
What is the structure of an essentially 8 overlapping beta alpha beta motif?
- 8 stranded parallel barrel concentric with an outer barrel of 8 alpha helices
- Each Beta strand is approximately antiparallel to the succeeding alpha helix and all inclined at around the same angle to the barrel axis.
In TIM barrel the side chains that point inward from the alpha helices interdigitate with what?
with the side chains that point outward from the Beta strand.
A large fraction of TIM barrel’s side chains that point inward from alpha helices and outward from the Beta strand are those of what?
branched aliphatic residues like Ile, Leu, and val (which are non polar residues)
The sidechains of TIM that point inward from the Beta strands tend to be what?
- bulky and fill core of Beta barrel
- the sidechains that fill ends of barrel are in contact with solvent thus are polar
- whereas sidechains that fill center of barrel are out of contact with solvent and tend to be nonpolar
In alpha Beta barrels the alpha and beta domain both do what?
consist of 2 layers of polypeptide backbone sandwiching a hydrophobic core
alpha beta barrels is the most common fold assumed by whom?
Enzymes
Open Beta sheet folds consist of what?
central parallel or mixed Beta sheet flanked on both sides by alpha helices that form right handed cross over connections between successive parallel Beta strands
Open Beta sheets do not follow their order in the peptide sequence but rather?
have long cross overs that reverse the direction of succeeding sections of sheet and turns it upside down , thereby putting its helical crossovers on the opposite side of the sheet than a regular beta sheet.
Open Beta sheets are also known as what?
Double wound sheets
Double wound sheets are what?
consist of 3 layers of polypeptides backbone interspersed by regions of hydrophobic side chains
How do the layers of polypeptides differ for Open Beta sheets, Alpha domains, Beta domains and alpha-Beta domains
- For open Beta sheets you have 3 polypeptides
- For alpha beta barrels you have 4 polypeptides
- 2 polypeptides for alpha helices
- 2 polypeptides for Beta sheets
Domains with parallel sheets are what on both sides?
Hydrophobic on both sides of the sheets
Domains with antiparallel sheets are what?
Hydrophobic on only one side.
The fact that parallel sheets are hydrophobic on both sides and antiparallel sheets are hydrophobic on only one side suggest what?
Parallel sheets offer more stability in this manner probabyl compensating for reduced strength of their nonlinear hydrogen bonds relative to their linear hydrogen bonds of antiparallel sheets.
What geometric constraints are there on open Beta sheets?
Few on the number of strands
- obsered 4-10
- 6 strands most common
What is the topological switching point?
The position on open Beta sheet which the chain reverse its winding direction
Where does the topological switching point occur?
Can occur between any consecutive alpha helix and Beta strand, double wound sheets can have many different folds.
How many switch points can occur?
Several can occur
The open Beta sheet is most common domain structure in what?
Globular proteins
In open Beta sheet some Beta strands may run antiparallel to do what?
Form mixed sheets
What is the function of disulfide bonds?
stabilizes third dimensional structure
When do disulfide bonds form?
As proteins fold to its native conformation
Almost all proteins with disulfide bonds are secreted where?
To more oxidized extracellular destinations where their disulfide bonds are effective in stabilizing tertiary structure of proteins
In what part of the bond is disulfide bonds form? why?
The endoplasmic reticulum because unlike other cellular compartment it has an oxidizing environment.
Any partial unfolding of the structure does what?
Destabilizes the remaining structure which must simultaneously sollapse to the random coil.
the temperature at the midpoint of the narrow temperature range that causes protein denaturing is called what?
The temperature melting point
Most proteins hae Tm values well below what?
100 degrees C
What are the four key ways to denature a protein?
1) high temperature
2) pH variation
3) Detergents
4) High concentration of water-soluble organic substances
How does pH cause denaturation of proteins?
pH variations alters the ionization states of amino acid side chains which changes protein charge distributions and H bonding requirements
How do detergents cause denaturation of proteins?
detergents hydrophobically associate with the nonpolar residues of a protein, thereby interfering with the hydrophobic interactions responsible for the protein’s native structure.
How do high concentrations of water-soluble organic substances denature proteins?
interferes with hydrophobic forces stabilizing protein structure through their own hydrophobic interactions with water.
aliphatic alcohols are examples of what?
water-soluble organic substances
Organic substances with several hydroxyl groups are realtively poor what? why?
poor denatures because of their H bonding ability renders them less disruptive of water structure
Ethylene, glycol and sucrose are all what?
organic substances with several hydroxyl groups thus poor denatures
Some salts such as (NH4)2SO4 and KH2PO4 do what to native protein structure?
stabilizes the native proteins structure which raises Tm.
Some salts like KCl and NaCl do what to native protein structure?
have little effect
Some salts like KSCN and LiBr does what to native protein structure?
Destabilizes it
What are the common ions that denature proteins?
- I-
- ClO4-
- SCN -
- Li+
- Mg 2+
- Ca 2+
- Ba 2+
The Hofmeister series that tend to denature proteins are called what?
chaotropic
Chaotropic agents do what to nonpolar sustances in water
increases solubility
Chaotropic agents act as denaturing agents how?
ability to disrupt hydrophobic interactions.
Substances that stabilize proteins do so how?
By strengthen hydrophobic forces, thus increasing the tendency of water to expel proteins.
The spatial arrangement of polypeptide subunits of a polypeptide is a protein’s what?
Quaternary Structure
proteins with identical subunits are called what?
the proteins are called oligomers and the subunits are called what protomers.
What does it mean by hemoglobin being a dimer?
oligomer of 2 protomers (protein of identical 2 subunits)
Leucine Zipper Motif
Coiled-coil interaction between two amphiphathic alpha helices
Collagen consists of non standard amino acids derived from what?
standard amino acid side chains after translation
Ascorbic acid is what?
A co-factor
The enzymes involved in post-translational modification require what?
Ascorbic acid as a co-factor
Deficiency of vitamin C leads to what?
Scurvy
What characterizes scurvy?
Lesions in collagen rich connective tissue:
- gums
- skin
- blood vessels
Collagen consists of what?
triple helix of left handed polyproline II helices
Each layer of the triple helix contain what residues?
- G
- P
- Hyp residue
What fibrous material is extensively glycosylated?
Collagen
Collagen is extensively what?
cross-linked
How is collagen arranged in the tendons
parallel bundles
How is the collagen arranged in skin?
Sheets of fibrils layered at many angles
How is collagen arranged in cartilage?
No distinct arrangement
How is collagen arranged in the cornea?
planar sheets stacked crossways so as to minimize light scattering
Mutations in genes for collagen or enzymes involved in processing collagen may cause what?
numerous genetic disease
keratin is classified as either
alpha keratin or beta keratin
A hair cell contains packed _____
macrofibrils
Macrofibrils are orientated in hair how?
orientated parallel to the hair fiber
Macrofibrils are constructed from what?
Microfibrils
How do the Microfibrils construct macrofibrils?
cemented together by an amorphous protein matrix of high sulfur content.
alpha keratin polypeptides form closely associated pairs of alpha helices in which each pair is composed of what?
a type I and type II keratin chain twisted in parallel into a left handed coil
The assembly of alpha keratin polypepetides have what structure? why?
coiled coil structure because each alpha helix axis itself follow a helical path.
The conformation of alpha keratin’s coiled coil is a consequence of its what?
primary structure
Alpha keratin polypeptides has a normal 5.4 A repeat distance of each alpha helix in the pair is what?
tilted with respect to axis of this assembly yeilding 5.1 spacing
The central ~310 residue segment of each polypeptide chain has what?
has a heptad (7 residues) psuedorepeat, a-b-c-d-e-f-g with nonpolar residues predominating at positions a and d.
Since an alpha helix has 3.6 residues per turn alpha keratin’s a and d residues so what?
Line up on one side of the alpha helix to form a hydrophobic strip that promotes its lengthwise association with a similar strip on the another alpha helix
What types of residues hae a strong tendency to associate?
Hydrophobic residues.
Coiled coil are common somponents of what proteins?
Globular and fibrous
What causes alpha keratin to form a coiled coil?
the slight discrepancy between 3.6 residues per turn of a normal helix and ~ 3.5 residues repeat of alpha keratin’s hydrophobic strip
Keratine is rich is what type of residue? Which do what?
Cys residues which form disulfide bonds that cross-link adjacent polypeptide chains.
Keratin being rich in cys residues account for what?
Keratin’s resistance to stretching and insolubility
Keratin is refered to as “soft” or “hard” according to what?
Sulfur contents
What makes Hard keratin less pliable than soft keratin?
This is because disulfide bonds resist any forces trying to deform them. The disulfide bonds can be reductively cleaved with mercaptans.
Hair curled can be set in a “permanent wave” how?
The disulfide bonds are first cleaved by mercaptans, curled then an application of an oxidizing agent which reestablishes the disulfide bonds in the new “curled” conformation is used.
The clothes moth larva have high concentrations of mercaptans in its digestive tract. Allowing it to do what?
digest keratin
The inherited skin diseases epidermolysis bullosa simplex (EBS) and epidermolytic hyperkeratosis (EHK) are characterized by what?
skin blisters arising from ruptured epidermal basal cells and suprabrasal cells repsectively caused by mechainical stress that would normally be harmelss but in these individuals keartin defects occur resulting in loss of skin integrity
Collage is a major stress-bearing component of what?
Collagen
Collagen occurs in virtually what?
Every tissue
Collagen has distinct amino acid composition which is what?
- ~ 1/3rd of its residues are Gly
- another 15-30% of them are pro and 4-hydroxypropyl (Hyp)
What other residues are common in collagen just in smaller amounts than the 3 major residues? When are these residues incorporated?
3- Hydroxypropyl
and 5-Hydroxylysyl (Hyl); Incorporated after polypeptide synthesis when certain pro residues are converted to hyp
How are Hyp residues formed
After polypeptide synthesis when certain pro residues are converted to Hyp in a reaction catalyzed by enzyme prolyl hydroxylase
Why would some residues of pro possiblly transform to hyp?
Hyp confers stability on collagen possibly by intramolecular hydrogen bonds that involve bridging water molecules.
If collagen is synthesized under conditions that inactivate prolyl hydroxylase what happens to collagen?
It loses native conformation (denatures) at 24 degrees C where as normal collagen denatures at 39 degrees Celsius.
Heat denatured collagen is called what?
Gelatin; normal collagen denatures at 39 degrees C.
Proyl hydroxylase requires what?
Ascorbic acid (Vitamin C)
Skin lessions, blood vessel fragility and poor wound healing are all symptoms of what?
Scurvy
The amino acid sequence of bovine collagen alpha 1 (I) which is similar to other collagen consists of what?
monotonously repeating triplets of sequence Gly-X-Y over a continously repeating triplets sequence Gly-X-Y over 1011-residue stretch of its 1042-residue polypeptide chain
- X often pro
- Y often Hyp
In bovine collagen alpha 1 (I) X is often?
most often pro (~28%)
In bovine collagen alpha1 (I) Y is often?
most often Hyp (~38%)
some times also Hyl both restricted due to specificity of molecules of Hyp and Hyl.
The high Gly, pro and Hyp content of collagen suggest what?
its polypeptide back bone conformation resembles those of proglycine II and polyproline II helices
Collagen has 3 polypeptide chains that are arranged how?
parallel and wind around each other in right handed twist to form triple helical structure
How did (pro-Hyp-Gly)10’s structure explain the residue arrangement of collagen?
In this structure the 5th Gly is replaced by Ala and every 3rd residue of each polypetide chain passes through the center of the triple helix, which is so crowded that only a Gly side chain can fit there. Therefore this crowding explains absolute requirement for Gly at every 3rd position of a collagen polypeptide chain.
Other the collagen structure requiring gly to be at every 3rd position on a collagen polypeptide chain due to crowding what else is required?
Requires that the three polypeptide chains be staggered so that the Gly, X and Y residues from the three chains occur on similar levels.
The staggered polypeptide groups of collagen are orientated how?
Such that the N-H group of each Gly makes a strong hydrogen bond with the carbonyl oxygen of an X (pro) residue on the neighboring chain.
What is responsible for Collagen’s tensile strength?
Collagen being well-packed, rigid and being triple helix.
What types of collagen are there?
I, II, III, V, XI
Type I collagen is packed how?
In hexagonal array with collagen molecules staggered parallel to fibril axis.
What is the driving force for the assembly of collagen molecules into a fibril?
by the added hydrophobic interactions within the fibrils
Collagen contains covalently atached carbohydrates in amount from ?
~0.4 to 12% by weight depending on tissue of origin
The covalently attached carbohydrates consist mostly of what and are covalently attached how?
glucose, galactose, and their disaccharides are covalently attached to collagen at its hyl residues by specific enzymes.
Carbohydrates in collagen are found where? suggesting they may have a role in what?
Found in the “hole” regions of collagen fibrils which suggest that they are involved in directing fibril assembly.
Why can’t the cross links in collagen be disulfide bonds like they are in keratin?
Because collagen is almost devoid of cys residues
Collagen’s insolubility in solvents that disrupt hydrogen bonds is because of what?
It is both intramolecularly and intermolecularly covalently cross-linked
What are the cross links in collagen derived from?
Lys and His side chains.
What enzyme is implicated in cross -linking process?
Lysyl oxidase; a Cu-containg enzyme that converts Lys residues to those of aldehyde allysine.
How many side chains in Collagen involved in cross linking can be covalently bonded to each other? Are these cross links random?
Up to four side chains; No cross links are not random they occur near N and C termi of colalgen molecules.
Lathyrisms shows the importance of what compinent of collagen? How?
Importance of cross-linking; causes serious abnormalities of bones, joints, and large blood vessels which are caused by increased fragility of collagen fibers.
The degree of cross linking of collagen from a particular tissue increases with what?
Age of animal
What meat is tougher : that from younger animals or that of older animals? why?
Older animals because collagen cross linking increases with age of animal
Individual molecules of collagen called tropocollagen can only be extracted from what?
the tissues of very young animals
