Quiz 6 Flashcards
1
Q
globular
A
soluble
2
Q
fibrous
A
insoluble
3
Q
primary level
A
sequence, covalent connection
4
Q
secondary level
A
local structures, H bonds
5
Q
tertiary level
A
overall 3D shape, all weak forces
6
Q
quaternary level
A
subunit organization for multiple polypeptide chains
7
Q
2,3,4 structures of proteins are formed and stabilized by
A
weak forces
8
Q
how are the 2,3,4 structures of protein stabilized?
A
- hydrophobic bonds are formed wherever possible [directional]
- hydrophobic interactions drive protein folding [water entropy]
- ionic interactions are abundant on protein surfaces [opposite charges]
- van der Waals interactions are everything [best packing]
9
Q
the tertiary structure or
A
fold of a protein
10
Q
constraints in secondary structure
A
the planar character of the peptide group limits the conformational flexibility of the polypeptide chain
11
Q
the alpha helix and the beta sheet allow
A
the polypeptide chain to adopt favorable phi and psi angles and to form hydrogen bonds
12
Q
fibrous proteins
A
contain long stretches of regular secondary structure, such as the closed coils in a keratin and the stacked b sheets in b keratin
13
Q
all peptide structure is based on the
A
amide plane
14
Q
phi is the rotation angle around the
A
Ca-NH bond
15
Q
psi is the rotation angle around the
A
Ca-CO bond
16
Q
due to steric hinderance
A
some phi and psi angles are forbidden
17
Q
G.N ramachandran
A
was the first to demonstrate the value of plotting phi, psi combinations from known protein structures
18
Q
the entire path of the peptide backbone is know if
A
all phi and psi angles are specified
19
Q
ramachandran plot
A
shows sterically allowed values for the angles phi and psi
20
Q
conformation
A
changing shape without breaking a bond
21
Q
configuration
A
requires breaking of a bond
22
Q
secondary structures are the local backbone structures that are stabilized by
A
hydrogen bonds
- a helices
- b sheet
- b turns
23
Q
the a helix
A
- stabilized by h bonds between backbone C=O and H-N groups
- because of amino acid chirality, the a helix has a right handed twist
24
Q
H bonds between the amide carbonyl group of
A
Cai and the amide nitrogen [H] of Cai+4
25
pitch includes
3.6 residues[one turn], and at a 1.5A rise per amino acid residue, is equal to 5.4 A high
26
the a helix continued
- right handed twist
- residues per turn: 3.6
- rise per residue: 1.5A
- rise per turn, "pitch": 3.6 x 1.5A = 5.4A
- h bonds between the amide carbonyl group and the amide nitrogen H
27
based on allowed phi-psi angles,
prolines angles are too restrictive
glycines angles are too permissive, flexible
28
B pleated sheets are composed of
B strands
29
antiparallel strands are connected by
a short turn
30
parallel strands are connected by
a longer loop
31
parallel b sheets are
less stable, bc they have imperfect H bond angles therefore >5 strands are requires
32
antiparallel b sheets
have straight short H bond, making them more stable. therefore <5 strands are required to form a sheet
33
the b turn or reverse turn
- allows the peptide chain to reverse reaction
- proline and glycine are prevalent in b turns
- carbonyl c of one residue is H bonded to the amide proton of a residue three residues away : C=O of a1 bonds with H-N of a4
34
fibrous proteins are usually
- insoluble[hair doesn't dissolve in water]
they play a structural role in nature
35
3 types of fibrous proteins are discussed here
1. a keratin
2. b keratin
3. collagen
36
a keratin
- a fibrous protein found in hair, fingernails, claws, horns and beaks.
- heptad repeat[7]: (a-b-c-d-e-f-g)n , where a and d are non polar, and b, c, e, f, and g are polar amino acid residues
- this primary structure promotes association of a helices to form coiled coils
37
the coiled coil is a
bundle of a helices wound into a superhelix
38
the left handed twist of the superhelix
reduces the number of resides per turn to 3.5 so that the positions of the side chains repeat every 7 residues called a heptad repeat of hydrophobic residues
39
b keratin
fibrous protein that forms extensive b sheets
40
b keratin are found in
silk fibers and bird feathers
41
b keratin have
- alternating sequence of two residues [GLY-ALA OR SER)n
- since side chains of a b sheet extend alternately above and below the plane of the sheet, this places all glycine on one side and all alanine or serines on the other side
42
stacking sheets give silk strength due to close packing van der Waals, this allows
glycine on one sheet to stack with glycine on an adjacent sheet, and on the other side ALA/SER residues mesh knobs into holes with another sheet
43
collagen helix
the principal component of connective tissue(tendons, cartilage, bones, teeth)
- three intertwined polypeptide chains
44
the collagen triple helix, 2 structure
- long stretches of the 3 among-acid repeat [GLY- PRO-PRO/HyP)n
- the unusual amino acid composition of collagen is unsuited for right handed a helices or b sheets
- much more extended than a helix with a rise per residue of 2.9A, 3.3 residues per turn
45
collagen triple helix
- unusual left handed helices wrap with a right handed superhelical twist
46
Poly(Gly-Pro-Pro) a collagen like
right handed superhelix composed of three left handed helical chains
47
in a collagen triple helix, every third residue faces the center of the helix
only glycine fits here
48
glycine, proline and HyP suit
the constraints of phi and psi
49
a keratin (hair and claw)
coiled coil has a "heptad repeat" 7 amino acid residues (a, b, c, d, e, f, g)n, where a and d are non polar and pack knobs into holes
50
b keratin (silk and feather)
stacked B sheets structure has an alternating repeat (Gly/Ala/Ser)n, where glycine sides pack extremely close together and Ala/Ser sides pack together, knobs into holes
51
collagen triple helix (bone, teeth)
has a (Gly-Pro-HyPro)n repeat that forms an elongated left handed helical structure that tightly intertwines three strands in a right handed super helix with glys packed inside
52
non polar residues tend to occur in
the protein interior and polar residues on the exterior
53
a proteins tertiary structure consist of secondary structural elements that combine to form
motifs and domain
54
throughout evolution,
a proteins structure Is more highly conserved than its sequence
55
globular proteins
are more numerous than fibrous proteins, and are more spherical
56
globular proteins functional diversity comes from
- the large number of folded structures that polypeptides adopt
- the varied chemistry of the side chains of the 20 amino acids
57
tertiary structure of globular proteins [PRINCIPLES]
- helices abd sheets make up the core
- most polar residues face the outside of the protein and interact with the solvent
- most hydrophobic residues face the interior of the protein
- van der Waals packing of residues is close
- the empty space in the form of small cavities allow for motion
58
principles learned from looking at atomic structures solved by NMR and X-ray crystallography
- large number H bonds
- helices and sheets often pack close together
- peptide segments between secondary structures tend to be short and direct
- proteins fold to form most stable structures
59
stability arises mainly from
1. formation of large numbers of intramolecular h bonds
2. reduction in the surface area accessible to solvent: COMPACT STRUCTURE
60
why do a helices and beta sheets form the core
- protein core is hydrophobic
- polar N-H and C=O groups of the peptide backbone must be neutralized in the hydrophobic core
61
the extensively h bonded nature of a helices and b sheets is ideal for
neutralizing the backbone amides in the hydrophobic core of globular proteins
62
the helices and sheets in the core of a globular protein family
are typically constant and conserved in sequence and structure
63
the protein surface is different in many ways
1. protein surface composed of short loops and tight turns.loop/turn sequences are more variable in protein families
2. the surface is a complex and irregular landscape of different structural elements
4. interactions are the basis for enzyme-substrate binding, cell signaling, and immune responses and all other protein functions
64
segments that are not helices or sheets are referred to as
random coil
- most of these segments are neither coiled nor random
65
structure of random coil segments are stabilized by side-chain
tertiary interactions with the rest of the protein
66
a helices on a protein surface are usually
- amphiphilic, with polar and charged residues facing the solvent and non polar residues facing the interior
67
some a helices are
hydrophobic and buried in the protein interior
68
some helices are
polar and entirely solvent exposed
69
domains
compact, folded protein structures that are usually stable by themselves in aqueous solution
70
multidomain proteins typically are the
sum of the functional properties and behaviors of their constituent domains
71
motifs
are small folding topologies found in a diversity of proteins
72
the need to bury hydrophobic residues inside the protein leads to
formation of layers of structure in the protein
73
more than half the known globular proteins have
two layers of backbone, with one hydrophobic core [this is the minimum for folded domains]
74
these intrinsically disordered proteins
do not possess uniform structural properties but are still essential for cellular function
75
these proteins are characterized by a nearly complete
lack of structure, with high flexibility adopt well defined structures in complexes with their target proteins are characterized by an abundance of polar residues and a lack of hydrophobic residues
76
proteins with quaternary structure contain
- multiple subunits [each its own polypeptide chain]
77
subunits are usually arranged symmetrically
- open and closed
78
what are the forces quaternary association?
- typical Kd for two subunits: 10^-8, 10^-16, tight binding
- entropy loss due to association of subunits is unfavorable [negative entropy]
- entropy gain for water molecules due to burial hydrophobic groups is very favorable [positive entropy]
79
open symmetry
the structure of a typical microtubule, showing the arrangement of the a and b monomers of the tubular dimer
80
advantages of quaternary structure
1. stability
2. genetic economy
3. assembly of catalytic sites between subunits
4. cooperativity
81
protein stability depends primarily on
hydrophobic effects and secondarily on electrostatic interactions and h bonds
82
protein structure and function
- structure depends on sequence and on weak non covalent forces
- the number of protein folding patterns is large but finite
- structures of globular proteins are marginally stable (G= -5 to -10 kj)
- marginal stability facilitates motion
- motion enables function
83
the cellular environment imposes constraints on
the weak forces that preserve protein structure and function
84
denaturation
loss of structure and function
85
proteins can be denatured by
heat or cold in some cases
- high conc of chaotropic agents, guanidinium HCl and urea
86
a folding protein follows a
pathway from high energy and high entropy to low energy and low entropy thus these state functions are at odds keeping delta G of folding small
87
molecular chaperones assist
protein folding via an ATP dependent mechanism
88
amyloid diseases result from
protein misfoldingg
89
what factors play a role in protein folding processes?
1. secondary structures
2. hydrophobic collapse
3. long-range interactions
4. molten globule
5. van der Waals packing
90
why are chaperones needed if the information for folding is inherent in the sequence?
- to protect from diseases caused by protein misfolding
- to protect newly formed proteins
