Chapter 6: Proteins: Three-Dimensional Structure Flashcards
1
Q
What is the order of the 4 structures of a protein?
A
Primary, Secondary, Tertiary, Quaternary
2
Q
What is the primary structure?
A
the linear sequence of amino acids in the protein/amino acid sequence in a polypeptide chain
3
Q
What is the secondary structure?
A
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
4
Q
What is the tertiary structure?
A
the three-dimensional structure of an entire polypeptide, including its side chains/one complete protein chain (β chain of hemoglobin)
5
Q
What is the quaternary structure?
A
the spatial arrangement of its subunits./ the four separate chains of hemoglobin assembled into an oligomeric protein
6
Q
A The Planar Peptide Group Limits What and Why?
A
Polypeptide Conformations because of its rigid planar structure and it has a partial double bond character due to resonance
7
Q
Which conformations do peptide groups assume?
A
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
8
Q
Which conformation is more stable and why?
A
Trans because of the steric interference between neighboring side chains in cis
9
Q
when is steric interference reduced
A
this steric interference is reduced in peptide bonds to Pro residues, so ∼10% of the Pro residues in proteins follow a cis peptide bond.
10
Q
Torsion Angles/dihedral angles/rotation angles between Peptide Groups Describe? and where
A
Polypeptide Chain Conformations. around the CαN bond ( ϕ ) and the CαC bond ( ψ ) of each residue
11
Q
Another name for backbone
A
main chain
12
Q
what is a backbone
A
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
13
Q
conformations degrees
A
trans, ω ≈ 180°, and cis, ω ≈ 0°.
14
Q
Which Diagram Indicates Allowed Conformations of Polypeptides?
A
The Ramachandran
15
Q
how does a peptide bond form
A
When the amino group of an amino acid combines with the carboxyl group of another amino acid, a peptide bond is formed.
16
Q
the most common regular secondary structures?
A
𝛂 Helix and the 𝛃 Sheet
17
Q
structure of an α helix? each turn contains how many amino acids?
A
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.
18
Q
structure of a β sheet?
A
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,
19
Q
2 types of a β pleated sheet ?
A
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).
20
Q
which strand of β sheet is more stable?
A
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.
21
Q
compare and contract α helix and the β sheet
A
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.
22
Q
what are the reverse turns or β bends
A
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.
23
Q
what are the reverse turns or β bends
A
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.
24
Q
what are the two kinds of proteins based on their morphology?
A
Fibrous
Globular
25
2 Fibrous proteins discussed?
Keratin and Collagen
25
2 Fibrous proteins discussed?
Keratin and Collagen
26
Describe 𝛂 Keratin, what are the two types?
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.
27
difference between fibrous and globular
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.
28
collagen structure
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
29
amino acid composition of collagen
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
30
what is collagen
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.
31
Keratin forms what kind of bonds that collagen doesn't
disulfide bonds contains Cys so it cross links to adjacent polypeptide chains unlike collagen resulting in collages poor solubility.
32
most proteins are ?
globular
33
Which Proteins Have Repeating Secondary Structures
Fibrous
34
Which Proteins Have Nonrepetitive Structures
Globular
35
What BEST distinguishes irregular secondary structure from regular secondary structure?
Unlike regular secondary structure, successive residues in irregular secondary structure do not have the same backbone configuration.
36
what happens in the tertiary structure?
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.
37
What are the 3 methods used to determine the positions of atoms in proteins? *********
X-Ray crystallography, NMR spectroscopy, and cryo-electron microscopy
37
What are the 3 methods used to determine the positions of atoms in proteins?
X-Ray crystallography, NMR spectroscopy, and cryo-electron microscopy
38
What does X-Ray crystallography do?
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
39
what do X-rays specifically image and why
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.
40
Most Crystalline Proteins Maintain Their what kind of Conformations.
native
41
why do Most Protein Crystal Structures Exhibit Less than Atomic Resolution.
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
42
a crystal structure analysis depends on?
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.
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?
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
44
Most Crystalline Proteins Maintain what kind of conformations
native ,crystalline proteins assume very nearly the same structures that they have in solution:
45
NOSEY function
Nuclear Overhauser spectroscopy provides interatomic distances for protons that are close in space, although they may be far apart in the protein sequence.
46
How does cryo-electron microscopy work
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.
47
what is nmr
is the only method that allows the determination of three-dimensional structures of proteins molecules in the solution phase.
48
Side Chain Location Varies with what?
Polarity
49
Where are the AA side chains in globular proteins locate/distributed
-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.
50
Tertiary Structures Contain Combinations of what kind of structure
Globular proteins—each with a unique tertiary structure—are built from combinations of secondary structural elements.
51
what are motifs/supersecondary structures
Groupings/interactions between secondary structural elements
occur in many unrelated globular proteins:
52
. The most common form of supersecondary structure is? and how does it work
the 𝛃 𝛂 𝛃 motif
which an α helix connects two parallel strands of a β sheet
53
the second type of supersecondary structure?
the 𝛃 hairpin motif, consists of antiparallel strands connected by relatively tight reverse turns
54
the third type of supersecondary structure?
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
55
the fourth type of supersecondary structure?
Greek key motif
a β hairpin is folded over to form a 4-stranded antiparallel β sheet.
56
what can most proteins be classified as?
as 𝛂 , 𝛃 , or 𝛂 / 𝛃 .
57
difference between the 3 types of proteins
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).
58
The α, β , and α/ β classes of proteins can be further categorized according to their ?
topology; that is, according to how their secondary structural elements are connected. barrels B and AB barrels
59
Polypeptide chains containing more than ∼200 residues usually fold into two or more globular clusters known as
domains
60
large polypeptides form?
domains
61
Domains often have a specific function such as the binding of a small molecule.
Consequently, many domains are structurally independent units that have the characteristics of small globular proteins.
62
tertiary structure is more conserved that?
sequence
63
what stores important protein structural data
The Protein Data Bank
64
what makes the quaternary structure different than the others
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.
65
List the advantages of multiple subunits in proteins.
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).
66
Why can’t proteins have mirror symmetry?
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.
67
Do subunits associate covalently or noncolavenlty
noncovalently
68
quaternary structures jave 2 or more?
polypeptide chains (subunits) / oligomers
69
what are protomers
identical subunits
70
how many subunits does hemoglobin have
4,
has the subunit composition α 2β2
71
The contact regions between subunits resemble?
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.
72
how are subunits arranged
symmetrically
rotational symmetry
73
simplest type of rotational symmetry?
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.
74
what is dihedral symmetry
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.
75
fibrous and globular play what kind of roles in the body
Fibrous plays a structural roel in the body
Globular involved in metablooic processes
76
What all forces stabilize proteins?
Hydrophobic effects, electrostatic interactions, disulfide bonds, and metal ions
77
which force has the greatest effect on protein stability
hydrophobic effect
78
hydrophobic's effect on proteins?
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.
79
The combined hydrophobic and hydrophilic tendencies of individual amino acid residues in proteins can be expressed as
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
80
The greater a side chain’s hydropathy, the more likely it is to occupy the___ of a protein,
interior
81
what kinds of electrostatic interaction force stabilize a protein
van der Waals because these forces act only over short distances and hence are lost when the protein is unfolded.
82
why do hydrogens have minor contributions to protein stability
This is because hydrogen-bonding groups in an unfolded protein form hydrogen bonds with water molecules.
83
what are the oppositely charged groups in proteins
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.
84
how do disulfide bonds contribute to protein stability
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.
85
how do metal ions stabilize some small domains
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.
86
why can proteins undergo denaturation?
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.
87
in what 4 ways can proteins be denatured?
-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,
88
what are chaotropic agents guanidinium ion and urea,
the most commonly used protein denaturants. Chaotropic agents are ions or small organic molecules that increase the solubility of nonpolar substances in water.
89
proteins can be denatured as well as?
renatured or denatured reversibly
renature spontaneously
90
Comformational flexibility is also known as?
breathing allows small molecules to diffuse in and out of the interior of certain proteins. because proteins are dynamic
91
Why would it be advantageous for a protein or a segment of a protein to lack defined secondary or tertiary structure?
Increased flexibility to perform unhindered conformational search when binding to target molecules
92
do proteins have a fixed and rigid structure?
proteins are flexible and rapidly fluctuating molecules whose structural mobilities are functionally significant.
93
do proeitns contain unfolded regions?
yeah An entire protein or a long polypeptide segment (>30 residues) may lack defined structure in its native state
94
intrinsically disordered proteins
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).
95
what is protein disulfide isomerase's role in protein folding
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.
96
describe the protein folding pathway
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
97
A folding protein follows a pathway from high energy and high entropy to
low energy and low entropy.
98
how do molecular chaperones assist in protein folding
molecular chaperones are proteins that assist the covalent folding or unfolding and the assembly or disassembly of proteins
99
what are the four types of molecular chaperones
Hsp70, trigger factor, chaperoning, and Hsp90
100
what is Hsp70?
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.
101
What is the trigger factor?
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.
102
What are the chaperoning?
form large, multisubunit, cagelike assemblies in both prokaryotes and eukaryotes. They bind improperly folded proteins and induce them to refold inside an internal cavity.
103
What is Hsp90?
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.
104
most chaperones require
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.
105
what does GroEL/ES chaperoning do
-functions as a protein folding cage
-Forms Closed Chambers in Which Proteins Fold
106
what Drive the Conformational Changes in GroEL/ES.
ATP Binding and Hydrolysis
107
advantage of chaperones
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.?/
108
what is caused by protein misfiling?
diseases
109
what are amyloid?
aggregates of hydrophobic centers
109
what are amyloid?
aggregates of hydrophobic centers
110
Amyloid-𝛃 Protein Accumulates which disease?
in Alzheimer’s Disease.
It is characterized by brain tissue containing abundant amyloid plaques (deposits) surrounded by dead and dying neurons
111
Prion Diseases Are Infectious TorF
True
112
Amyloid Fibrils are what kind of structures?
𝛃 Sheet Structures.
113
Diseases caused by protein misfolding include?
the amyloidoses, Alzheimer’s disease, Parkinson’s disease, and the transmissible spongiform encephalopathies (TSEs), all of which may be transmitted by prions.
