Chapter 6: Proteins: Three-Dimensional Structure

Question 1

What is the order of the 4 structures of a protein?

Answer 1

Primary, Secondary, Tertiary, Quaternary

Question 2

What is the primary structure?

Answer 2

the linear sequence of amino acids in the protein/amino acid sequence in a polypeptide chain

Question 3

What is the secondary structure?

Answer 3

The secondary structure arises from the hydrogen bonds formed between atoms of the polypeptide backbone that form into 3 main structures: a helixes b sheets b turns
when the sequence of amino acids are linked by hydrogen bonds
side chains not included

Question 4

What is the tertiary structure?

Answer 4

the three-dimensional structure of an entire polypeptide, including its side chains/one complete protein chain (β chain of hemoglobin)

Question 5

What is the quaternary structure?

Answer 5

the spatial arrangement of its subunits./ the four separate chains of hemoglobin assembled into an oligomeric protein

Question 6

A The Planar Peptide Group Limits What and Why?

Answer 6

Polypeptide Conformations because of its rigid planar structure and it has a partial double bond character due to resonance

Question 7

Which conformations do peptide groups assume?

Answer 7

Trans Conformation- successive C atoms are on opposite sides of the peptide bond joining them

Cis Conformation- successive C αatoms are on the same side of the peptide bond

Question 8

Which conformation is more stable and why?

Answer 8

Trans because of the steric interference between neighboring side chains in cis

Question 9

when is steric interference reduced

Answer 9

this steric interference is reduced in peptide bonds to Pro residues, so ∼10% of the Pro residues in proteins follow a cis peptide bond.

Question 10

Torsion Angles/dihedral angles/rotation angles between Peptide Groups Describe? and where

Answer 10

Polypeptide Chain Conformations. around the CαN bond ( ϕ ) and the CαC bond ( ψ ) of each residue

Question 11

Another name for backbone

Answer 11

main chain

Question 12

what is a backbone

Answer 12

The backbone just refers to the polypeptide chain apart from the R groups
The backbone or main chain of a protein refers to the atoms that participate in peptide bonds, ignoring the side chains of the amino acid residues. The backbone can be drawn as a linked sequence of rigid planar peptide groups

Question 13

conformations degrees

Answer 13

trans, ω ≈ 180°, and cis, ω ≈ 0°.

Question 14

Which Diagram Indicates Allowed Conformations of Polypeptides?

Answer 14

The Ramachandran

Question 15

how does a peptide bond form

Answer 15

When the amino group of an amino acid combines with the carboxyl group of another amino acid, a peptide bond is formed.

Question 16

the most common regular secondary structures?

Answer 16

𝛂 Helix and the 𝛃 Sheet

Question 17

structure of an α helix? each turn contains how many amino acids?

Answer 17

In an α helix, the carbonyl (C=O) of one amino acid is hydrogen bonded to the amino H (N-H) of an amino acid that is four down the chain. (E.g., the carbonyl of amino acid 1 would form a hydrogen bond to the N-H of amino acid 5.) This pattern of bonding pulls the polypeptide chain into a helical structure that resembles a curled ribbon, with each turn of the helix containing 3.6 amino acids. The R groups of the amino acids stick outward from the α helix, where they avoid steric interference with the backbone and each other.

Question 18

structure of a β sheet?

Answer 18

two or more segments of a polypeptide chain line up next to each other, forming a sheet-like structure held together by hydrogen bonds. The hydrogen bonds form between carbonyl and amino groups of backbone, while the R groups extend above and below the plane of the sheet,

Question 19

2 types of a β pleated sheet ?

Answer 19

The strands of a β pleated sheet may be Parallel, pointing in the same direction (meaning that their N- and C-termini match up),
Or Antiparallel, pointing in opposite directions (meaning that the N-terminus of one strand is positioned next to the C-terminus of the other).

Question 20

which strand of β sheet is more stable?

Answer 20

Antiparallel

parallel β sheets are less stable than antiparallel β sheets,possibly because the hydrogen bonds of parallel sheets are distorted compared to those of the antiparallel sheets (Fig. 6-9).

not related but β Sheets containing mixtures of parallel and antiparallel strands frequently occur.

Question 21

compare and contract α helix and the β sheet

Answer 21

Like the α helix, the β sheet uses the full hydrogen-bonding capacity of the polypeptide backbone. In β sheets, however, hydrogen bonding occurs between neighboring polypeptide chains rather than within one, as in an α helix.

Question 22

what are the reverse turns or β bends

Answer 22

β-Turns are one of the most common structural motifs in proteins and change the direction of the peptide backbone by nearly 180°, allowing the peptide chain to fold back onto itself.

Question 23

what are the reverse turns or β bends

Answer 23

β-Turns are one of the most common structural motifs in proteins and change the direction of the peptide backbone by nearly 180°, allowing the peptide chain to fold back onto itself.

Question 24

what are the two kinds of proteins based on their morphology?

Answer 24

Fibrous
Globular

Question 25

2 Fibrous proteins discussed?

Answer 25

Keratin and Collagen

Question 25

2 Fibrous proteins discussed?

Answer 25

Keratin and Collagen

Question 26

Describe 𝛂 Keratin, what are the two types?

Answer 26

Keratin is a coiled coil.is a mechanically durable and relatively unreactive protein that occurs in all higher vertebrates. It is the principal component of their outer epidermal (skin) layer and its related appendages, such as hair, horn, nails, and feathers.

Keratins have been classified as either α keratins, which occur in mammals, or β keratins, which occur in birds and reptiles. Humans have more than 50 keratin genes that are expressed in a tissue-specific manner.

Question 27

difference between fibrous and globular

Answer 27

Fibrous proteins are generally composed of long and narrow strands and have a structural role (they are something)
Globular proteins generally have a more compact and rounded shape and have functional roles (they do something)
fibrous has little to no tertiary structure.

Question 28

collagen structure

Answer 28

the collagen polypeptide assumes a left-handed helical conformation with about three residues per turn. Three parallel chains wind around each other with a gentle, right-handed, ropelike twist to form the triple-helical structure of a collagen molecule

Question 29

amino acid composition of collagen

Answer 29

Nearly one-third of its residues are Gly; another 15 to 30% of its residues are Pro and 4-hydroxyprolyl (Hyp). 3-Hydroxyprolyl and 5-hydroxylysyl (Hyl) residues also occur in collagen, but in smaller amounts.
Gly-X-Y over a segment of ∼1000 residues, where X is often Pro and Y is often Hyp

Question 30

what is collagen

Answer 30

occurs in all multicellular animals, is the most abundant vertebrate protein. Its strong, insoluble fibers are the major stress-bearing components of connective tissues such as bone, teeth, cartilage, tendon, and the fibrous matrices of skin and blood vessels. A single collagen molecule consists of three polypeptide chains.

well-packed, rigid, triple-helical structure is responsible for its characteristic tensile strength.

Question 31

Keratin forms what kind of bonds that collagen doesn’t

Answer 31

disulfide bonds contains Cys so it cross links to adjacent polypeptide chains unlike collagen resulting in collages poor solubility.

Question 32

most proteins are ?

Answer 32

globular

Question 33

Which Proteins Have Repeating Secondary Structures

Answer 33

Fibrous

Question 34

Which Proteins Have Nonrepetitive Structures

Answer 34

Globular

Question 35

What BEST distinguishes irregular secondary structure from regular secondary structure?

Answer 35

Unlike regular secondary structure, successive residues in irregular secondary structure do not have the same backbone configuration.

Question 36

what happens in the tertiary structure?

Answer 36

The tertiary structure of a protein describes the folding of its secondary structural elements and specifies the positions of each atom in the protein, including those of its side chains.

Question 37

What are the 3 methods used to determine the positions of atoms in proteins? *******

Answer 37

X-Ray crystallography, NMR spectroscopy, and cryo-electron microscopy

Question 37

What are the 3 methods used to determine the positions of atoms in proteins?

Answer 37

X-Ray crystallography, NMR spectroscopy, and cryo-electron microscopy

Question 38

What does X-Ray crystallography do?

Answer 38

a technique that directly images molecules
a crystal of the molecule to be imaged (e.g., Fig. 6-20) is exposed to a collimated beam of X-rays and the resulting diffraction pattern, which arises from the regularly repeating positions of atoms in the crystal, is recorded by a radiation detector or, now infrequently, on photographic film

Question 39

what do X-rays specifically image and why

Answer 39

X-Rays interact almost exclusively with the electrons in matter, not the nuclei.
An X-ray structure is therefore an image of the electron density of the object under study.

Question 40

Most Crystalline Proteins Maintain Their what kind of Conformations.

Answer 40

native

Question 41

why do Most Protein Crystal Structures Exhibit Less than Atomic Resolution.

Answer 41

it is highly hydrated 40-60% water,necessary for the structural integrity of the protein crystals, because water is required for the structural integrity of native proteins themselves

Question 42

a crystal structure analysis depends on?

Answer 42

the crystal’s resolution limit. a crystal structure analysis depends on the crystal’s resolution limit. Indeed, the inability to obtain crystals of sufficiently high resolution is a major limiting factor in determining the X-ray crystal structure of a protein or other macromolecule.

Question 43

Most protein crystal structures are too poorly resolved for their electron density maps to reveal clearly the positions of individual atoms (e.g., Fig. 6-23). Nevertheless, what can be obtained?

Answer 43

the distinctive shape of the polypeptide backbone usually permits it to be traced, which, in turn, allows the positions and orientations of its side chains to be deduced

Question 44

Most Crystalline Proteins Maintain what kind of conformations

Answer 44

native ,crystalline proteins assume very nearly the same structures that they have in solution:

Question 45

NOSEY function

Answer 45

Nuclear Overhauser spectroscopy provides interatomic distances for protons that are close in space, although they may be far apart in the protein sequence.

Question 46

How does cryo-electron microscopy work

Answer 46

Cryo-Electron Microscopy Directly Images Macromolecular Structures

a hydrated sample is cooled to nearliquid nitrogen temperatures (–196°C) so rapidly (in a few milliseconds) that the water in the sample does not have time to crystallize (which would destroy the sample), but rather assumes a vitreous (glasslike) state. Consequently, the sample remains hydrated and retains its native structure. This, together with ongoing technological and theoretical advances in electron microscopy, has permitted, in recent years, the direct visualization of large molecular complexes, such as ribosomes, at near-atomic resolution (as little as 3.0 Å). Cryo-EM therefore holds great promise for determining the structures of fragile or flexible complexes that are difficult to crystallize and too large to visualize by NMR methods.

Question 47

what is nmr

Answer 47

is the only method that allows the determination of three-dimensional structures of proteins molecules in the solution phase.

Question 48

Side Chain Location Varies with what?

Answer 48

Polarity

Question 49

Where are the AA side chains in globular proteins locate/distributed

Answer 49

-The nonpolar residues Val, Leu, Ile, Met, and Phe occur mostly in the interior of a protein, out of contact with the aqueous solvent.The hydrophobic effects that promote this distribution are largely responsible for the three-dimensional structure of native proteins.
-The charged polar residues Arg, His, Lys, Asp, and Glu are usually located on the surface of a protein in contact with the aqueous solvent. This is because immersing an ion in the virtually anhydrous interior of a protein is energetically unfavorable.
-The uncharged polar groups Ser, Thr, Asn, Gln, and Tyr are usually on the protein surface but also occur in the interior of the molecule. When buried in the protein, these residues are almost always hydrogen bonded to other groups; in a sense, the formation of a hydrogen bond “neutralizes” their polarity. This is also the case with the polypeptide backbone.

Question 50

Tertiary Structures Contain Combinations of what kind of structure

Answer 50

Globular proteins—each with a unique tertiary structure—are built from combinations of secondary structural elements.

Question 51

what are motifs/supersecondary structures

Answer 51

Groupings/interactions between secondary structural elements
occur in many unrelated globular proteins:

Question 52

. The most common form of supersecondary structure is? and how does it work

Answer 52

the 𝛃 𝛂 𝛃 motif
which an α helix connects two parallel strands of a β sheet

Question 53

the second type of supersecondary structure?

Answer 53

the 𝛃 hairpin motif, consists of antiparallel strands connected by relatively tight reverse turns

Question 54

the third type of supersecondary structure?

Answer 54

In an 𝛂𝛂 motif, two successive antiparallel α helices pack against each other with their axes inclined. This permits energetically favorable intermeshing of their contacting side chains

Question 55

the fourth type of supersecondary structure?

Answer 55

Greek key motif
a β hairpin is folded over to form a 4-stranded antiparallel β sheet.

Question 56

what can most proteins be classified as?

Answer 56

as 𝛂 , 𝛃 , or 𝛂 / 𝛃 .

Question 57

difference between the 3 types of proteins

Answer 57

Some proteins, such as E. coli cytochrome b consist only of α helices spanned by short connecting links and are therefore classified as 𝛂 proteins. Others, such as immunoglobulins, which contain the immunoglobulin fold (Fig. 6-29b), are called 𝛃 proteins because they have a large proportion of β sheets and are devoid of α helices. Most proteins, however, including lactate dehydrogenase (Fig. 6-29c) and carboxypeptidase A (Fig. 6-12), are known as 𝛂/ 𝛃 proteins because they largely consist of mixtures of both types of secondary structure (proteins, on average, contain ∼31% α helix and ∼28% β sheet).

Question 58

The α, β , and α/ β classes of proteins can be further categorized according to their ?

Answer 58

topology; that is, according to how their secondary structural elements are connected. barrels B and AB barrels

Question 59

Polypeptide chains containing more than ∼200 residues usually fold into two or more globular clusters known as

Answer 59

domains

Question 60

large polypeptides form?

Answer 60

domains

Question 61

Domains often have a specific function such as the binding of a small molecule.

Answer 61

Consequently, many domains are structurally independent units that have the characteristics of small globular proteins.

Question 62

tertiary structure is more conserved that?

Answer 62

sequence

Question 63

what stores important protein structural data

Answer 63

The Protein Data Bank

Question 64

what makes the quaternary structure different than the others

Answer 64

Many proteins are made up of a single polypeptide chain and have only three levels of structure (the ones we’ve just discussed). However, some proteins are made up of multiple polypeptide chains, also known as subunits. When these subunits come together, they give the protein its quaternary structure.In general, the same types of interactions that contribute to tertiary structure (mostly weak interactions, such as hydrogen bonding and London dispersion forces) also hold the subunits together to give quaternary structure.

Question 65

List the advantages of multiple subunits in proteins.

Answer 65

Easier repair by replacing the flawed subunit.
*The site of manufacture can be different from the site of assembly into final product.
*more economical because less genetic information is needed.
*In the case of enzymes, its active sites are more structurally stable when the protein size is large, and increasing the size through association of identical subunits is more efficient than increasing the length of its polypeptide chain since each subunit has an active site.
*Subunit construction provides capability to regulate function(turn on/off function by assembling and disassembling the multimer).

Question 66

Why can’t proteins have mirror symmetry?

Answer 66

Proteins can not have mirror inversion symmetry because to achieve such symmetries proteins need to have both L- and D- amino acids, which is not the case. converting chiral L residues to D residues. Thus, proteins can have only rotational symmetry.

Question 67

Do subunits associate covalently or noncolavenlty

Answer 67

noncovalently

Question 68

quaternary structures jave 2 or more?

Answer 68

polypeptide chains (subunits) / oligomers

Question 69

what are protomers

Answer 69

identical subunits

Question 70

how many subunits does hemoglobin have

Answer 70

4,
has the subunit composition α 2β2

Question 71

The contact regions between subunits resemble?

Answer 71

the interior of a singlesubunit protein: They contain closely packed nonpolar side chains, hydrogen bonds involving the polypeptide backbones and their side chains, and, in some cases, interchain disulfide bonds.

Question 72

how are subunits arranged

Answer 72

symmetrically
rotational symmetry

Question 73

simplest type of rotational symmetry?

Answer 73

cyclic symmetry,
protomers are related by a single axis of rotation (Fig. 6-34a). Objects with two-, three-, or n-fold rotational axes are said to have C2 , C3 , or C n symmetry, respectively. C 2 symmetry is the most common; higher cyclic symmetries are relatively rare.

Question 74

what is dihedral symmetry

Answer 74

a more complicated type of rotational symmetry, is generated when an n-fold rotation axis intersects a twofold rotation axis at right angles (Fig. 6-34b). An oligomer with D n symmetry consists of 2n protomers. D 2 symmetry is the most common type of dihedral symmetry in proteins.

Question 75

fibrous and globular play what kind of roles in the body

Answer 75

Fibrous plays a structural roel in the body
Globular involved in metablooic processes

Question 76

What all forces stabilize proteins?

Answer 76

Hydrophobic effects, electrostatic interactions, disulfide bonds, and metal ions

Question 77

which force has the greatest effect on protein stability

Answer 77

hydrophobic effect

Question 78

hydrophobic’s effect on proteins?

Answer 78

leads to the burial of non polar side chains to the interior of the protein, waters contact with the non polar is minimized
The aggregation of nonpolar side chains in the interior of a protein is favored by the increase in entropy of the water molecules that would otherwise form ordered “cages” around the hydrophobic groups.

Question 79

The combined hydrophobic and hydrophilic tendencies of individual amino acid residues in proteins can be expressed as

Answer 79

Hydropathies
-good predictors of which portions of a polypeptide chain are inside a protein, out of contact with the aqueous solvent, and which portions are outside

Question 80

The greater a side chain’s hydropathy, the more likely it is to occupy the___ of a protein,

Answer 80

interior

Question 81

what kinds of electrostatic interaction force stabilize a protein

Answer 81

van der Waals because these forces act only over short distances and hence are lost when the protein is unfolded.

Question 82

why do hydrogens have minor contributions to protein stability

Answer 82

This is because hydrogen-bonding groups in an unfolded protein form hydrogen bonds with water molecules.

Question 83

what are the oppositely charged groups in proteins

Answer 83

ion pair/salt bridge
about 75% of proteins
locate don the protein surface
contribute little to stability This is because the free energy of an ion pair’s charge–charge interactions usually fails to compensate for the loss of entropy of the side chains and the loss of solvation free energy when the charged groups form an ion pair.

Question 84

how do disulfide bonds contribute to protein stability

Answer 84

Disulfide bonds (Fig. 4-6) within and between polypeptide chains form as a protein folds to its native conformation
important for “locking in” a particular backbone folding pattern as the protein proceeds from its fully extended state to its mature form.

Question 85

how do metal ions stabilize some small domains

Answer 85

Metal ions may also function to internally cross-link proteins
ex: zinc fingers- 10 motifs,The Zn 2+ion allows relatively short stretches of polypeptide chain to fold into stable units that can interact with nucleic acids.

Question 86

why can proteins undergo denaturation?

Answer 86

The low conformational stabilities of native proteins make them easily susceptible to denaturation by altering the balance of the weak nonbonding forces that maintain the native conformation.

Question 87

in what 4 ways can proteins be denatured?

Answer 87

-heating causes a protein’s conformationally sensitive properties, such as optical rotation, viscosity, and UV absorption, to change abruptly over a narrow temperature range.
-pH variations alter the ionization states of amino acid side chains
-Detergents interfere with the hydrophobic interactions responsible for the protein’s native structure.
-CHAOTROPIC AGENTS guanidinium ion and urea,

Question 88

what are chaotropic agents guanidinium ion and urea,

Answer 88

the most commonly used protein denaturants. Chaotropic agents are ions or small organic molecules that increase the solubility of nonpolar substances in water.

Question 89

proteins can be denatured as well as?

Answer 89

renatured or denatured reversibly
renature spontaneously

Question 90

Comformational flexibility is also known as?

Answer 90

breathing allows small molecules to diffuse in and out of the interior of certain proteins. because proteins are dynamic

Question 91

Why would it be advantageous for a protein or a segment of a protein to lack defined secondary or tertiary structure?

Answer 91

Increased flexibility to perform unhindered conformational search when binding to target molecules

Question 92

do proteins have a fixed and rigid structure?

Answer 92

proteins are flexible and rapidly fluctuating molecules whose structural mobilities are functionally significant.

Question 93

do proeitns contain unfolded regions?

Answer 93

yeah An entire protein or a long polypeptide segment (>30 residues) may lack defined structure in its native state

Question 94

intrinsically disordered proteins

Answer 94

are characterized by sequences rich in certain polar and charged amino acids (Gln, Ser, Pro, Glu, Lys, Gly, and Ala) and lacking in bulky hydrophobic groups (Val, Leu, Ile, Met, Phe, Trp, and Tyr).

Question 95

what is protein disulfide isomerase’s role in protein folding

Answer 95

Enzyme that catalyzes rearrangement of disulfide bonds. Does this by making new bonds to break old bonds, freeing up cysteines to make the correct dissulfide bonds ,thus allowing proper protein folding

catalyse the formation of native disulfide bonds in protein folding pathways.

Question 96

describe the protein folding pathway

Answer 96

protein folding begins with the formation of local segments of secondary structure (α helices and β sheets).
Because native proteins contain compact hydrophobic cores, it is likely that the driving force in protein folding is what has been termed a hydrophobic collapse.
The collapsed state is known as a molten globule, a species that has much of the secondary structure of the native protein but little of its tertiary structure.
In the final stage of folding, which for small, singledomain proteins occurs over the next few seconds, the protein undergoes a series of complex rearrangements in which it attains its relatively stable internal side chain packing and hydrogen bonding while it expels the remaining water molecules from its hydrophobic core.

In multidomain and multisubunit proteins, the respective units then assemble in a similar manner, with a few slight conformational adjustments required to produce the protein’s native tertiary or quaternary structure.

A folding protein must proceed from a high-energy, high-entropy state to a low-energy, low-entropy state.

An unfolded polypeptide has many possible conformations (high entropy). As it folds into an everdecreasing number of possible conformations, its entropy and free energy decrease

Question 97

A folding protein follows a pathway from high energy and high entropy to

Answer 97

low energy and low entropy.

Question 98

how do molecular chaperones assist in protein folding

Answer 98

molecular chaperones are proteins that assist the covalent folding or unfolding and the assembly or disassembly of proteins

Question 99

what are the four types of molecular chaperones

Answer 99

Hsp70, trigger factor, chaperoning, and Hsp90

Question 100

what is Hsp70?

Answer 100

they facilitate the folding of newly synthesized proteins and reverse the denaturation and aggregation of proteins. Hsp70 proteins also function to unfold proteins in preparation for their transport through membranes and to subsequently refold them.

Question 101

What is the trigger factor?

Answer 101

a ribosome-associated chaperone in prokaryotes that prevents the aggregation of polypeptides as they emerge from the ribosome (Section 27-5A). Trigger factor and Hsp70 are the first chaperones a newly made prokaryotic protein encounters.

Question 102

What are the chaperoning?

Answer 102

form large, multisubunit, cagelike assemblies in both prokaryotes and eukaryotes. They bind improperly folded proteins and induce them to refold inside an internal cavity.

Question 103

What is Hsp90?

Answer 103

eukaryotic proteins that mainly facilitate the late stages of folding of proteins involved in cellular signaling (Chapter 13). Hsp90 proteins are among the most abundant proteins in eukaryotes, accounting for up to 6% of cellular protein under stressful conditions that destabilize proteins.

Question 104

most chaperones require

Answer 104

hydrolisis of ATP needed for when molecular chaperones operate bind to an unfolded or aggregated protein’s solvent-exposed hydrophobic surface and subsequently releasing it.

Question 105

what does GroEL/ES chaperoning do

Answer 105

-functions as a protein folding cage
-Forms Closed Chambers in Which Proteins Fold

Question 106

what Drive the Conformational Changes in GroEL/ES.

Answer 106

ATP Binding and Hydrolysis

Question 107

advantage of chaperones

Answer 107

Chaperones may reduce the effects of a mutation in a protein that would otherwise preclude its proper folding.

Subsequent mutations could then improve the protein’s folding efficiency and solubility, thereby reducing its dependence on chaperones and increasing its abundance. Thus, chaperones increase the range of mutations that are subject to Darwinian selection.?/

Question 108

what is caused by protein misfiling?

Answer 108

diseases

Question 109

what are amyloid?

Answer 109

aggregates of hydrophobic centers

Question 109

what are amyloid?

Answer 109

aggregates of hydrophobic centers

Question 110

Amyloid-𝛃 Protein Accumulates which disease?

Answer 110

in Alzheimer’s Disease.
It is characterized by brain tissue containing abundant amyloid plaques (deposits) surrounded by dead and dying neurons

Question 111

Prion Diseases Are Infectious TorF

Answer 111

True

Question 112

Amyloid Fibrils are what kind of structures?

Answer 112

𝛃 Sheet Structures.

Question 113

Diseases caused by protein misfolding include?

Answer 113

the amyloidoses, Alzheimer’s disease, Parkinson’s disease, and the transmissible spongiform encephalopathies (TSEs), all of which may be transmitted by prions.