Chapter 4-Three Dimensional Structure of Proteins Flashcards
1
Q
native conformations
A
3D shapes of proteins with biological activity
2
Q
primary structure
A
- the order in which the amino acids in a protein are linked by peptide bonds
- the 1D first step in specifying the 3D structure of a protein
3
Q
secondary structure
A
- the arrangement in space of the backbone atoms in a polypeptide chain
- alpha helix and beta pleated sheets
- contain repetitive interactions resulting from hydrogen bonding between the N-H and the carbonyl group of the peptide
- contains domains or supersecondary structures
4
Q
tertiary structure
A
-3D arrangement of all the atoms in the protein (including those in the sedition and in prosthetic groups)
5
Q
prosthetic groups
A
portions of proteins that do not consist of amino acids
6
Q
subunits
A
individual parts of the larger molecule
7
Q
quaternary structure
A
interaction of several polypeptide chains in a multisubunit protein
8
Q
what does the primary structure of a protein determine?
A
the 3D structure, which determines the properties
9
Q
hemoglobin is associated with what disease?
A
sickle cell anemia
10
Q
sickle cell anemia
A
- RBC can’t bind oxygen efficiently
- RBC lack sickle shape
- stem from a change in one amino acid residue
11
Q
domain
A
aka supersecondary structure
-specific clusters of secondary structural motifs in proteins
12
Q
what type of bonds in secondary structure?
A
hydrogen
13
Q
Ramachandran angles
A
used to designate rotations of the C-N (phi) and C-C (psi) bond
14
Q
alpha and beta pleated sheets are found in what structure
A
secondary
15
Q
alpha helix
A
- one of the most frequently encountered folding patterns in the protein backbone
- rodlike
- one polypeptide chain
16
Q
beta pleated sheets
A
- one of the most important types of secondary structure, in which the protein backbone is almost fully extended with hydrogen bonding between adjacent strands
- can give 2D array
- can involve 1+ more polypepetide chains
17
Q
why are alpha helices and beta sheets considered periodic structures?
A
they feature repeats at regular intervals
18
Q
Alpha helices are stabilized by
A
- hydrogen bonds parallel to the helix axis within the backbone of a single polypeptide chain
- hydrogen bonding is linear
19
Q
There are ____ residues for each turn of the helix
A
3.6
20
Q
pitch (linear distance between corresponding points on successive turns) is ____ A
A
5.4A
1A= 10-8cm=10-10m
21
Q
Disruptive forces in alpha helices
A
- Proline: creates bend in the backbone b/c of its cyclic structure
- strong electrostatic repulsion
- steric replusion: caused by bulky side chains
22
Q
in alpha helices, where do side chains lie?
A
outside the helix
23
Q
describe the peptide backbone in the B sheet
A
- completely extended
- hydrogen bonds can be formed between different parts of a single chain that is doubled back on itself or between different chains
24
Q
Hydrogens bonds are ______ to the direction of the protein chain in beta pleated sheets and ______ in the alpha helix
A
perpendicular; parallel
25
Three10 helix
three residues per turn and 10 atoms in the ring formed by making the hydrogen bond
26
B-Bulge
- common non-repetive irregularity found in antiparallel beta sheets
- occurs between two normal B structure hydrogen bonds
- involves 2 residues on one strand and 1 on another
27
what does a reverse turn often mark?
a transition between one secondary structure to another
28
reverse turn
parts of proteins where the polypeptide chain folds back on itself
29
motif
repetitive super secondary structure
30
what molecule is frequently encountered in reverse turns?
glycine: the single hydrogen of the side chain prevents crowding
31
list the super secondary structure
- beta alpha beta
- alpha alpha
- beta meander
- greek key
32
beta alpha beta
two parallel stands of B sheets are connected by a stretch of alpha helices
33
alpha alpha unit
- aka helix turn helix
- consists of two antiparallel alpha helices
- energetically favorable contacts exist between the side chains in the two stretches of helix
34
B meander
-antiparallel sheet is formed by a series of tight reverse turns connecting stretches of polypeptide chain
35
greek key
-antiparallel sheet doubles back on itself in a pattern
36
protein sequences that allow for B meander or greek key can often be found arranged into a B-barrel in
the tertiary structure of the protein
37
can motifs predict biological function?
no; they are found in proteins and enzymes with very dissimilar functions
38
type 1 reverse turn
residue 3 the side chain lies outside the loop
| any amino acid can be there
39
type 2 reverse turn
side chain of residue 3 has been rotated 180 degrees
residue 3 now on inside of loop
glycine must be residue 3
40
proline residue normally occupies what residue on the reverse turn
2
41
collagen
- component of bone and connective tissue
- consists of three polypoetide chains wrapped around eacahother in a triple helix
- either X-Pro-Gly or X-Hyp-Gly
- every third position must be Gly (inside the helix)
42
proline and hydroxyproline can constitute up to 30% of the residues in
collagen
43
how is hydroxyproline formed?
from proline by a specific hydroxylating enzyme after the amino acids are linked together
44
tropocollagen
- triple helical molecule
- 300nm long and 1.5nm diameter
- held together by hydrogen bonds
- each strand contains 800AA residues
45
T/F: amount of cross linking increases with age
true
46
collagen is both intramolecularly and intermolecularly linked by covalent bonds formed by
reactions of lysine and histidine residues
47
Scurvy
- result of fragile collagen (when proline is not hydroxylated to normal extent)
- bleeding of gums and skin discoloration
- deficient in Vitamin C
48
fibrous proteins
proteins whose overall shape is that of a long, narrow rod
49
globular proteins
- proteins whose overall shape is more or less spherical
- water soluble
- compact structures
- complex tertiary and quaternary structures
50
characteristics of tertiary structure
- 3D arrangement of all atoms
- side chains (arrangement of atoms inside and position)
- position of prosthetic groups
51
secondary and tertiary structure depends on ______ interactions
non-covalent
52
information about the location of disulfide links combined with primary structure gives
complete covalent structure of a protein
53
what two molecules lack disulfide bonds, but have metal ions? what metal ion?
myoglobin and hemoglobin; Fe(II) as part of a prostethic group
54
list the forces that stabilize the tertiary structure of proteins
- metal ion coordination
- hydrophobic interactions
- disulfide bond
- electrostatic interaction
- side chain hydrogen bonding
55
xray crystallography
experimental method for determining the 3D structure of proteins using crystals
56
NMR
method for determining the shape of proteins in a solution
| depends on H atoms
57
myoglobin
- globular protein
- 153 AA residues
- heme group
- compact structure (interior atoms close together)
- 8 alpha helices; no beta sheets
- 2 polar histidine residues on inside that interact with heme group and oxygen
58
heme
- iron-containing cyclic compound found in cytochromes, hemoglobin and myoglobin
- consists of metal ion Fe(II), protroporhrin ring
59
porphyrin part consists of
4 five membered rings based on pyrrole structure
| 4 rings linked by bridging methane groups
60
Fe(II)
- 6 coordination sites (4 sites occupied by nitrogen of pyrrole; 1 by nitrogen atoms in imidazole side chain of histidine residue F8; 1 by oxygen)
- forms 6 metal ion complexation bonds
61
the presence of what is required for myoglobin to bind to oxygen
heme
62
E7 histidine
streakily inhibits oxygen from binding perpendicularly to the heme plane; lies by binding site of oxygen
63
why does oxygen have imperfect binding to the heme group?
- more than 1 molecule can bind to the heme
- affinity of heme for CO2 is greater than oxygen (but is forced to bind at an angle)
- too perfect binding would defeat purpose of having the oxygen-carrying proteins
64
combination of both heme and protein is needed to bind
O2; without protein the iron of heme can be oxidized to Fe(III) and won't bind oxygen
65
denaturation
unraveling of the 3D structure (3level) of a macromolecules caused by breakdown of noncovalent interactions
66
reduction of disulfide bonds causes
extensive unraveling of 3 structure
67
how can proteins be denatured?
- heat
- change in pH
- binding of detergents
- urea & guanidine hydrochloride
- B mercaptoethanol
68
describe how heat causes denaturation
increase in temp, favors vibrations, energy of these vibrations disrupt the structure
69
describe how change in pH causes denaturation
at either extreme, charges are missing and so the electrostatic interactions that normally stabilize the protein are reduced
70
describe how binding of detergents causes denaturation
ex) SDS
- disrupt hydrophobic interactions
- if charged can disrupt electrostatic interactions
71
describe how urea & guanidine hydrochloride causes denaturation
- they form hydrogen bonds with the protein that are stronger than those within the protein
- disrupt hydrophobic interactions
72
describe how B mercaptoethanol causes denaturation
-reduces disulfide bridges to two sulfhydryl groups
73
dimers
molecules with two subuntis
74
oligomer
aggregate of several smaller units; bonding can be covalent or non
75
allosteric
property of a multisubunit proteins such that a conformational change in one subunit induces a change in another
76
how to chains of quaternary structure interact with eachother
electrostatic interactions, hydrogen bonds and hydrophobic interactions
77
hemoglobin
- allosteric protein
- tetramer (4 polypeptide chains, 2alpha/2beta that are identical)
- alpha chain: 141 residues
- beta chain: 153 residues
- heme
- four molecules of oxygen bind to 1 hemoglobin
78
binding of oxygen to hemoglobin exhibits
positive cooperativity
79
postive cooperativity
cooperative effect where by binding the first ligand to an enzyme or protein causes the affinity for the next to be higher (i.e.: once one O is bound it is easier for the next to bind)
80
oxygen binding curve of myoglobin
hyperbolic (rises quickly then levels off)
81
oxygen binding curve of hemoglobin
sigmodial (S shaped curve); characteristic of cooperative interactions
82
myoglobin has a higher percentage of _______ that hemoglobin at any level
saturation
83
function of myoglobin
oxygen storage
84
function of hemoglobin
oxygen transport; must be able to bind and release oxygen easily
85
alveoli of lungs
where hemoglobin must bind oxygen for transport, O2 pressure 100torr
so hemoglobin is 100% saturated with oxygen
86
capillaries of active muscle
O2 pressure 20torr; less than 50% saturation
| aka hemoglobin gives up oxygen here easily because need is great
87
in the bound (oxygenated) form of hemoglobin the B chains are
much closer to each other than that of the deoxygenated
88
What other molecules affect the affinity of hemoglobin for oxygen by alterating the proteins 3D shape?
H+ and C02 (bind to hemoglobin)
89
Bohr effect
- the effect of H+
- in actively metabolizing tissue (lower pH), hemoglobin releases oxygen and binds both CO2 and H+
- in the lungs (higher pH), hemoglobin hemoglobin releases CO2 and H+ and binds to oxygen
- in the presence of H+ and CO2, the oxygen binding capacity of hemoglobin decreases
90
2,3-bisphosphoglycerate (2,3-BPG)
- binds to hemoglobin in blood
- binding to hemoglobin is electrostatic
- lowers oxygen binding capacity when bound to hemoglobin
91
fetal hemoglobin
- fetus obtains oxygen from bloodstream of mom via placenta
| - has high affinity for oxygen
92
why does fetal hemoglobin have a higher oxygen binding capacity?
- presence of two polypeptide chains (HbF & HbA)
| - HbF binds less strongly to BPG than HbA
93
role of hydrophobic interactions
-protein folding into 3D shape `
94
what makes hydrophobic interactions favorable?
- spontaneous
| - entropy (S) increases when reactions occur
95
what diseases are caused by acculmulation of protein deposits from incorrect folding of hydrophobic regions?
Alzheimers
Parkinsons
Huntingtons
96
chaperones
prevents a protein from associating with another protein which it shouldn't or itself in negative ways
97
AHSP
globin chaperone that binds to alpha global (excess) and keeps it from aggravating with itself and delivers it to the B-globin
98
thalassemia
damaged red blood cells from excessive alpha chain aggravates
99
Prion diseases
- cause of mad cow
- cause of creutzfeldt jakobs
- comes about when normal form of PrP folds into PrPsc
100
what are prions
natural glycoproteins found in cell membrane of nerve tissue
101
abnormal prions have
more beta sheets
