Lecture 7 Flashcards
1
Q
What structure of proteins specify their function function?
A
3-D structure
2
Q
What is the primary structure?
A
- simple sequence of amino acids linked together via peptide bonds
3
Q
what is the secondary structure ?
A
- formed by regular folding patterns in specific regions of the protein
4
Q
What are the different patterns of secondary folding?
A
- alpha helix
- beta pleated sheet
- random coil or loop region
5
Q
What is the tertiary structure?
A
- regions of local structure are then coiled into an overall 3-D structure for entire polypeptide sequence
6
Q
What is Quaternary structure?
A
- not every protein has this structure
- protein molecules known as subunits assemble into a multimeric protein held together by weak forces
- structures are only present if a protein has multiple subunits associated together in its final form
7
Q
How are changes to amino acid sequence tolerated ?
A
- it depends on where they occur within the 3-D structure of the protein
8
Q
What are conservative and non conservative changes ?
A
- conservative –> preserve chemical properties
- nonconservative –> result in completely different side chain type or size
9
Q
What are the comparisons of the primary structure of sperm whale myoglobin vs. human myoglobin ?
A
- both 153 amino acids long
- similar in primary sequence but not identical, but still manage to have same function
- evolution has resulted in changes to amino acid sequences between the proteins
10
Q
what determines the protein primary structure?
A
the genetic code
11
Q
what is the genetic code?
A
- nucleotide triples, codons, used to code for each amino acid
- considered to be standard genetic code
12
Q
what are the possible combinations for codons ?
A
4^3 = 64 possible cominations with 4 nucleotides
13
Q
What are Pauling’s rules for secondary structure ?
A
- bond lengths and angles of aa and peptides must stay fairly consistent to those observed by diffraction studies
- no atoms should approach more closely than their Van de Waals radii
- six atoms in peptide-amid should be coplanar –> rotation is possible around bonds adjacent to alpha carbon
- some kind of noncovalent bonding is necessary to stabilize structure, usually hydrogen bonding
14
Q
What is the importance of rotation about single bonds in a polypeptide?
A
- rotation around these bonds allows protein backbone to fold into secondary and tertiary structures
15
Q
Around which bonds is rotation allowed around ?
A
- N amide – C alpha –> phi
- C alpha – C carbonyl –> psi
think of phi and psi bonds
16
Q
What are the most frequent forms of secondary structure that satisfy Pauling’s criteria? (Hint: most commonly observed)
A
- alpha helix
- beta pleated sheet
- most commonly observed secondary structures
17
Q
What are structures like for the alpha helix and beta pleated sheet ?
A
- in each structure the amide group is planar –> think of Pauling’s rules for secondary structure
- all amide protons and carbonyl carbons are involved in H bonding
18
Q
Structure of the alpha hellix
A
- Rod-like in structure
- R groups extend outwards
- C–O & N–H hydrogen bonding hold 2^0 structures in place
- right hand are the most common of helices
19
Q
What is the H-bonding patter of the alpha helix ?
A
- each of the carbonyls are bonded to an amide that is 4 residues removed
- Example: (1) C=O — H-N (5)
(2) C=O — H-N (6)
and so forth
20
Q
Structural features of the alpha helix for H bonding
A
- for the right handed helix 3.6 a.a –> meaning hydrogen bonds that form between amino acids is not exactly 4
- H-bond between every 3.6 (4) between the oxygen of the carboxyl group and the hydrogen of the amino group
- H bonds are parallel to axis of helix
- can be in hydrophobic or hydrophilic environments
- can even be amphipathic
21
Q
Structure of beta pleated sheets
A
- held together by hydrogen bonds
- fully extended; often in hydrophobic core of a protein
- can have amphipathic sheet where R groups point on inside and also outside
- distance between adjacent a.a. is 3.5
- parallel and anti-parallel beta sheets are possible
- -> unique H bonding properties
- -> antiparallel arrangement can arise by “hairpin folding” of a single strand
22
Q
structure of polypeptide (polyproline) II helix
A
- highly made up proline residues
- does not satisfy H bond requirements –> this is because helical nature is created by Proline kinks themselves
- left handed
- glycine are often found as well –> non polar, very small –> bc its so small it allows for all these kinks
23
Q
What are the positions of side chains in alpha helix and beta sheets ?
A
- can have amphipathic charateristics:
–> one face is hydrophobic and one is hydrophilic
Ex: an amphipathic alpha helix will have side chains of similar polarity every 3-4 residues ; whereas B-strand will have alternating polar and nonpolar side chains (2 hydrophilic, and 2 hydrophobic)
24
Q
T or F; Beta pleated sheets are usually twisted or wrapped into barrel structures
A
True
25
T or F; at phi = 0 degrees and psi = 0 degrees is a sterically allowed conformation
- False; it is a sterically nonallowed conformation
-- this is due to steric crowding: congestion caused by physical presence of surrounding ligands which may slow down or prevent reactions
26
What are Ramachandran plots?
- steric hindrance that excludes phi and psi combinations
| - allow us to describe which structures are sterically possible
27
Ranges of allowed psi and phi angles for Beta pleated sheet
phi: -150 to -100
psi: 120 to 160
phi bond: between amino group and alpha carbon
psi bond: between alpha carbon and carboxylic acid group
28
Ranges of allowed phi and psi angles for alpha helix?
phi: -70 to -60 degrees
psi: -50 to -40 degrees
- h bonding between every 4th amino acid right handed
29
Ranges of allowed psi and phi angles for 310 helix?
phi: -70 to -60 degrees
psi: -30 to -10 degrees
- h bonded every 3rd amino acid
30
Ranges of allowed psi and phi angles for polypeptide ii helix ?
phi: -80 to -60 degrees
psi: 130 to 160 degrees
-- H bond between very 5th amino acid
31
Secondary structure function
- help make up proteins to be fibrous (long and extended) or globular (blobs)
32
What type of protein is collagen?
- fibrous protein
- most plentiful protein in the vertebrates made up of proline and glycine
- each polypeptide is a left-handed helical structure which is Gly (every 3rd aa) Proline and Hydroxyproline
-- any other amino acid other than Gly would be too buly
-- cross-links between lysine residues form between helices to form a collagen fibril
-- hydrogen bonding between amide protons and carbonyl carbons, but hydroxyproline also links the triple helices
33
how does hydroxyproline make collagen tougher?
- by cross-linking strands
34
What is hydroxyproline?
- diff version of proline
| - has a hydroxyl group
35
What is the relationship between Vitamin C and hydroxyproline?
- enzymes that catalyze the hydroxylation of proline require Vitamin C to function
36
T or F; excessive vitamin C leads to scurvy, weaking collagen
False; it is extreme vitamin C deficiency, called scurvy, weakens collagen fibers because of reduced hydrogen bonding between collagen fiber chains; proline in this case cannot be hydroxylased
37
Characteristics of weakened collagen (scurvy)
- all of the following happen due to weak connective tissue:
--> deficiency disease: scurvy
--> deficiency symptoms: anemia, atherosclerotic plaques, pinpoint hemorrhages under skin, bone fragility, joint pain;
--> poor wound healing, frequent infections, bleeding gums, loosened teeth
--> muscle degeneration and pain, hysteria, depression, rough skin, blotch bruises
38
T or F; Tertiary structure shows conformation of the whole polypeptide in 3 dimensions?
True
39
T or F; tertiary structure is stabilized by majority covalent disulfide bonds between Cysteines
False; stabilized by noncovalent bonds and sometimes by covalent disulfied bonds between Cysteines
40
What types of bonds are included in tertiary structure?
- disulfide bond, hydrogen bond, salt bridges and more
41
True or False; proteins cannot be made up of more than one domain
False; proteins are made up of more than one domain
-- multiple domains more common in larger proteins
42
True or False; hairpin turns allow abrupt changes in polypeptide chain direction
True
43
What is a hairpin turn ?
- A hairpin is a special case of a turn, in which the direction of the protein backbone reverses and the flanking secondary structure elements interact.
44
T or F, It is energetically unfavorable to adopt a protein structure
False; it is favorable --> folding of a protein is a chemical reaction with a negative change in free energy if folding is to be spontaneous
45
Even though folding is more ordered why is it favorable?
- in an unfolded state water molecules are more ordered around structure --> causing folding to be more favorable
-- however the folding is not that stable and takes little to denature or unfold protein
46
True or False; protein structure is usually unstable and can be unfolded with slight increases in temperature
- True
