Protein structure, function, & mutations Flashcards
1
Q
Which part of the amino acid has a positive charge?
A
amino group
2
Q
Which part of the amino acid has a negative charge?
A
carboxyl group
3
Q
Which amino acids have a negative charge?
A
aspartic and glutamic acid
4
Q
What amino acids have a positive charge?
A
arginine, lysine and histidine
5
Q
Which amino acid has a phenol ring?
A
Tyrosine
6
Q
How is the hydrophobic core formed during folding?
A
from non polar side chains
7
Q
How are polar side chains exhibited on proteins after folding?
A
Project outwards to form hydrogen bonds with water
8
Q
polar molecule meaning
A
molecule with partial positive and negative charges - charged
9
Q
non-polar meaning
A
no charge
10
Q
Describe the effect of urea on proteins
A
Urea can denature proteins by direct interaction
11
Q
is the effect of urea on proteins reversible or irreversible?
A
reversible
12
Q
Describe Van der Waals
A
short range weak electrical attraction and repulsion
13
Q
Describe non-covalent interactions
A
electrostatic attraction between positively and negatively charged ions
14
Q
Types of secondary structure
A
alpha helix, beta sheet, random coil
15
Q
Which type of beta sheets has a continuous structure
A
anti-parallel
16
Q
describe the characteristics of protein domains
A
compact, stable, hydrophobic core
17
Q
Describe Green Fluorescent protein as a domain
A
very stable, formed from beta sheet structure
18
Q
What are the functions of GFP
A
biological research, labels specific proteins
19
Q
What is the PDZ domain
A
common structural domain found in signalling proteins of bacteria, yeast, animals etc
20
Q
Where is PDZ abundant?
A
brain and synapses
21
Q
What is the function of PDZ
A
mediate protein-protein interactions, and act as protein scaffolds
22
Q
Where does the PDZ mainly act as a protein scaffold
A
post synaptically
23
Q
Describe src tyrosine kinase
A
multi protein domain
24
Q
What are SH2 and SH3
A
Src tyrosine domains
25
What is the function of SH2
adds specificity to kinase
26
What does SH2 bind to
phosphorylated tyrosine residues
27
What is the function of SH3
adds specificity to kinase
28
What does SH3 bind to
proline rich regions in proteins
29
Describe quaternary structure
proteins in a multi protein complex
30
What do common structures in proteins indicate?
Common functions
31
What do tubulin subunits form
microtubules
32
What are the different structures of microtubules?
filaments, sheets, rings and tubes
33
What do protein-protein interactions require?
complementary surfaces
34
What drives coiled coil packing
hydrophobic interactions
35
Examples of proteins as molecular motors
myosin on actin, kinesin on microtubules, polymerases on DNA
36
What type of amino acids are in membrane spanning domains
non-polar
37
Describe the the terminals in single pass type 1 membrane proteins
N terminus is extracellular, C terminus is intracellular
38
Which domain is largest in single pass type 1 membrane proteins
Extracellular domain
39
Describe the relationship of tumour necrosis factor with the membrane
tethered to membrane by lipid modifications
40
Examples of post-translational modifications
phosphorylation, glycosylation, palmitoylation, ubiquitination and acetylation
41
Where do post-translational modifications occur?
on reactive side chains
42
Describe lipid modifications
variety of lipophilic covalent attachments
43
Examples of lipid modifications
Acylation, Prenylation, GPI anchors
44
Describe acylation
intracellular addition of long chain fatty acids to cysteine residues
45
Describe prenylation
intracellular addition of farnesyl groups
46
Where do GPI anchors occur
extracellularly
47
Is acylation reversible?
YES
48
Describe palmitoylation
covalent attachment of fatty acids usually to cysteine
49
TRUE or FALSE, palmitoylation is irreversible
FALSE
50
Describe the bonding in a farnesyl anchor
thioether linkage between cysteine and prenyl groups
51
Describe the bonding in palmitoyl anchors
thioester linkage between cysteine and palmitic group
52
What is the general function of lipid anchors?
target and stabilise association of proteins with the membrane
53
What is the function of GTPase Ras
transmit signals within cells
54
What lipid modifications can be performed on ras?
farnesylation and palmitoylation
55
What is the function of lipid modifications on RAS
regulate cycling of Ras between membranes
56
What is the function of depalmitoylation of Ras
allows cycling back to endomembranes
57
What is the function of GTP
signalling molecule
58
what is synaptosomal-associated protein 25
t-SNARE protein
59
How is synaptosomal associated protein 25 modified
palmitoylation
60
what is the function of palmitoylation on synaptosomal associated protein 25
allows recycling between PM, endosomes and golgi
61
Where are disulphide bonds typically found?
secreted proteins like anti-bodies
62
Describe proteolytic processing
active hormone or enzyme is post-translationally cleaved
63
what is the outcome of proteolytic processing
mature functional molecule
64
What does glycosylation modify
extracellular proteins (generally)
65
What are the two types of glycosylation
N-linked and O-linked
66
What is the function of N-linked glycosylation
cellular protection
67
example of N-linked glycosylation
mucins in mucous
68
describe O-linked glycosylation
attachment via hydroxyl group of serine
69
What type of proteins does O-linked glycosylation modify?
intracellular proteins
70
Example of glycosylation patterns
blood groups
71
What is released from the kinase following protein phosphorylation
ADP
72
What amino acids does protein phosphorylation usually occur on
serine, threonine and tyrosine
73
What does protein phosphorylation do
converts a hydroxyl group into negatively charged phosphate groups
74
Where on proteins does phosphorylation occur?
binding surface
75
What does protein phosphorylation prevent/promote?
protein interactions
76
What type of change is phosphorylation to the protein
conformational change can alters nature of binding surface
77
Describe GTP binding proteins
heterotrimers
78
What is the function of GTP binding proteins
Bind guanine nucleotides GDP and GTP
79
Where are GTP binding proteins located
inner surface of plasma membrane and transmembrane receptors
80
Describe ubiquitination
attachment of new protein by addition of chain of ubiquitin to lysine residues
81
What are the types of ubiquitination
mono-ubiquitylation, multi-ubiquitylation, and poly-ubiquitylation
82
Which type of ubiquitination is the most common?
poly-ubiquitylation
83
What is the function of mono-ubiquitylation
histone regulation
84
what is the function of multi-ubiquitylation
endocytosis
85
what is the function of poly-ubiquitylation
proteasomal degradation, DNA repair, and further modification
86
What is the function of sorting siganls
direct target proteins to correct destination
87
What happens if a protein has NO sorting signal
remains in the cytosol
88
What is a signal peptidase?
protease that chops off signal peptide
89
What is the function of a signal peptidase
allows release of mature protein into ER lumen
90
What type of proteins can cross the ER
water soluble proteins
91
What happens to transmembrane proteins in the ER
partially cross the ER and become embedded in the membrane
92
When does protein folding occur
translocation
93
What influences protein folding
primary structure of the protein
94
What type of bonding stabilises protein folding
covalent bonding
95
What type of bonding is mainly involved with protein folding
non-covalent bonding
96
What is the function of disulphide bonds in protein folding
aid folding and stabilisation of final structure
97
What is the function of molecular chaperones?
assist protein folding
98
What do molecular chaperones bind to
misfolded exposed hydrophobic regions
99
How do heat shock proteins assist protein folding?
hydrolyse ATP
100
When is protein misfolding common
at high temperatures
101
What is the difference between Hsp70 and Hsp60
Hsp60 acts on fully synthesised proteins, Hsp70 works during protein synthesis
102
How does Hsp70 work?
binds to regions of hydrophobic amino acids, applies mechanical force to aid correct folding
103
How does Hsp60 work?
Acts as an isolation chamber, applies mechanical force
104
Describe the Hsp60 chamber
lining that prevents protein binding
105
What can misfolding lead to
aggregation
106
Where do protein aggregations accumulate
extracellular matrix
107
Diseases associated with protein aggregations
Alzheimer's and prion diseases
108
What is the effect of aggregation on neurons
neurons cant regenerate, so detrimental to brain function
109
Example of stable beta sheet aggregates
amyloid fibrils
110
what causes amyloid fibrils to aggregate
cross linking
111
What is the function of amyloid fibrils
store peptide hormones in secretory granules
112
Give examples of prion diseases
Creutzfeldt-jakob disease, bovine spongiform encephalopathy
113
Where are prion proteins located?
outside of PM, mainly in neurons
114
What is the function of prion proteins?
maintaining myelination of peripheral nervous system
115
What is different about abnormal prion proteins?
resist protease action, so aren't degraded
116
Where does protein destruction occur?
proteasome
117
What proteins are targeted for destruction?
old and damaged, incorrectly assembled, proteins whose concentrations change depending on cell state
118
How are proteins marked for destruction?
covalent attachment of ubiquitin
119
What binds to ubiquitylated proteins
proteasome cap
120
What is the effect of proteases on proteins targeted for destruction?
cleave the protein into short peptides
121
What is ubiquitination mediated by?
ubiquitin conjugating enzymes and ubiquitin ligases (E2 & E3)
122
What is the function of ubiquitin ligases (E3)?
bind to degradation signals on proteins
123
What does ubiquitin ligases E3 enable ubiquitin conjugating enzymes E2 to do
Enables E2 to link a polyubiquitin chain to lysine on target protein
124
What type of DNA is conserved? (introns or exons)
Exons
125
Mutations in which cell type are inherited?
Germline
126
What type of mutations are dominant
gain of function
127
What type of mutations are recessive
loss of function
128
Describe an amorphic mutation
complete loss of function
129
Describe hypo-morphic mutations
reduction of function
130
Describe a hyper morphic mutation
increase in protein function
131
Describe an antimorphic mutation
Protein interferes with function of wild type protein
132
Describe a neo morphic mutation
acquisition of a new function or ectopic expression or function
133
Describe a synonymous mutation
does not disturb the protein sequence
134
Describe a non-synonymous mutation
structural change of protein
135
What is an indel
insertions of deletions of sequence
136
What is the effect of an indel
adds residues into protein sequences
137
What are the types of mutation (non-sense) etc
transition, transversion, mis-sense, non-sense, neutral, silent, frameshift
138
Describe a transition mutation
change of base from purine to purine
139
Describe a transversion mutation
substitution of purine to pyrimidine
140
Describe a missense mutation
change in amino acid
141
describe a non-sense mutation
change to code for a stop codon
142
What is the effect of a non-sense mutation
premature termination of translocation, incomplete polypeptide
143
What is a neutral mutation
changes from one AA to another with non functional effect
144
What does wobble base pairing cause
spontaneous mutation
145
describe deamination
chemical change - cytosine is deaminated into uracil
146
describe depurination
chemical change - adenine or guanine is lost from DNA backbone
147
What type of mutations do X-rays and gamma rays induce?
point mutations
148
Why does ionising radiation (x-rays) induce point mutations
high energy
149
What is the effect of UV on DNA
replication problems
150
Why does UV cause DNA replication problems
low energy so causes photochemical changes in DNA
151
What are the types of chemical induced mutations
base analogues, base modifiers, intercalating reagents
152
Example of a base analogue
5-bromouracil
153
What type of mutations do base analogues cause
transition mutations
154
What is the effect of base modifiers
chemically modify structure of bases
155
what is the effect of intercalating agents
insert themselves in-between bases in DNA
156
what type of mutations do base modifiers cause
transition mutations
157
What type of mutations do intercalating agents cause?
frameshift or deletion
158
What causes sickle cell anaemia?
recessive mutation
159
what mutation causes sickle cell anaemia
single point missense mutation at residue 6 in the beta chain
160
how can sickle cell anaemia mutation be identified?
electrophoresis
161
What is an advantage of being a heterozygous carrier for malaria
tolerance to malaria
162
what is the function of the cystic fibrosis transmembrane conductance regulator
transport chloride, regulate ion concentration in extracellular fluid
163
where are mutations in GTPase Ras normally found
cancer cells
164
What is the effect of mutations on ras
impairs the intrinsic GTPase activity
165
What are the types of chromosomal mutations
deletion, inversion, duplication, translocation
166
Describe the Philadelphia chromsome
translocation of a piece of chromosome 22 to chromosome 9 causing fusion of 2 genes
167
What is the function of lipid modifications
help to bind proteins to membranes
