Lecture 4-Proteins Flashcards
(135 cards)
1
Q
The human body can generate .. ……. different types of proteins from —— genes?
A
2 million
20,000 genes
2
Q
What’s a polypeptide?
A
Amino acid monomers linked together by peptide bonds
3
Q
Polypeptides >40 AA can what?
A
Fold into a defined shape
4
Q
What determines the shape + function of a protein?
A
Protein sequence of AA
5
Q
Structural protein
A
Support
Collagen
6
Q
Storage protein
A
Storage
Casein
7
Q
Transport protein
A
O2 transport
Haemoglobin
8
Q
Hormonal protein
A
Metabolism
Insulin
9
Q
Receptor protein
A
Cellular response
Beta-Adrenergic receptor
10
Q
Contractile protein
A
Movement
Actin, Myosin
11
Q
Defensive protein
A
Protection
Antibodies
12
Q
Enzymatic protein
A
Catalysis
Digestive enzymes
13
Q
Proteinogenic AA
A
All proteins are composed of 20 standard AA
14
Q
Apart from ……. , the C in all AA is a …. …..
A
GLYCINE
chiral centre
15
Q
What’s a chiral centre?
A
An atom in a molecule that is bonded to 4 different chemical species
16
Q
AA can exist as 2 …………?
A
Enantiomers
17
Q
What are enantiomers?
A
Mirror images (L + D) = non-superimposable
18
Q
What form of enantiomers dominates amino acids?
A
L
19
Q
Physicochemical properties of an AA is determined by what?
A
R group
20
Q
R groups can be:
A
Nonpolar
Polar
Acidic
Basic
21
Q
Which R groups are hydrophobic?
A
Nonpolar
22
Q
Which R groups are hydrophilic?
A
Polar
Acidic
Basic
23
Q
Which AA is a secondary amino group + why?
A
PROLINE , because its attached to 2 carbons
24
Q
What AA have non-polar R groups?
A
Glycine Alanine Valine Leucine Isoleucine Methionine Phenylalanine Tryptophan Proline
25
What AA have basic R groups?
Lysine
Arginine
Histidine
26
What AA have polar R groups?
```
Tyrosine
Asparagine
Glutamine
Serine
Threonine
Cysteine
```
27
What can polar R groups do?
form H bonds with similar side chains + peptide bonds
28
What can CYS residues form?
Disulphide bridges
29
How does polypeptide chains form?
Achieved via linkage of -COOH + -NH2 groups via dehydration synthesis
30
What are peptide bonds?
Rigid + planar
31
Why are peptide bonds rigid + planar?
Because of bond resonance
32
Are peptide bonds trans or cis?
Trans
33
Except for glycine, why is rotation at C usually limited in cis form?
Because of STERIC CLASHES between bulky R groups
34
Primary structure
AA sequence
35
Secondary structure
- Interactions between adjacent AA ,so parts of polypeptide chains to take on regular patterns of H bonding:
- Alpha helices
- Beta pleated sheets
36
Tertiary structure
3D folding of a single polypeptide chain
37
Quaternary structure
Assembly of multiple proteins into a complex
38
AA sequence from ........ to ........
N-terminus to C-terminus
39
What is the primary structure determined by?
The DNA sequence of the gene for each protein
40
Why do primary structures of proteins dictate the final protein structure?
Because the sequential arrangement of R groups influencing subsequent structures
41
Describe the alpha helix secondary structure?
- Coiled rod-like structure
- Most common secondary structure
- Flexible + elastic
42
What can disrupt alpha helix structure?
Proline
43
Where is alpha helices abundant in?
Haemoglobin
44
Where is alpha helices absent in?
Chymotrypsin
45
How is the alpha helix stabilised?
The extensive intra-chain hydrogen bonding
46
How many AA are in the alpha helix per turn?
3.6
47
What bond forms the backbone of alpha helices?
Peptide bonds
48
Why do R groups project outwards in alpha helices?
To avoid steric hindrance
49
C=O is the . ........
| N-H is the . ...........
H acceptor
| H donor
50
Describe the beta plated sheet?
- Flat sheets
- Pleated
- short runs of 5-10 AA
- Can be parallel / anti-parallel / mixed
- Strands are = almost fully extended
- Strong
- Resilient
51
What are multiple sheets connected by in beta pleated sheet?
Short turns / hairpin loops
52
Side chains of beta sheets are arranged?
ALTERNATELY ON OPPOSITE SIDES of the strand
53
Are beta sheets more flexible than alpha helices?
YES
54
Length of beta sheets in a protein ranges from ........... residues?
2-22 residues
55
What is the function of loops/random coils?
Connect secondary structural elements
56
Where are loops/random coils normally located?
On the surface
57
Describe loops/random coils?
Rich in polar + charged residues
58
Loops/random coils lengths?
2-20 residues
59
What are loops/random coils frequently part of?
Enzyme active sites
60
How are loops/random coils different to other secondary structures?
LESS CONSERVED
61
Differences between structurally similar proteins typically occur in ...
loops
62
Beta hairpin motif
2 adjacent anti-parallel beta strands joined by a hairpin loop
63
What is the simplest supersecondary structure?
the beta hairpin motif
64
Where are beta hairpin motifs most common in ?
Globular proteins
65
What is the specific function of beta hairpin motif?
No specific function
66
Helix loop helix motif
2 alpha helices connected by a loop
67
What are the functions of helix loop helix motif?
1) DNA binding e.g. c-Myc
| 2) Ca2+ binding motif e.g. Calmodulin
68
Where are helix loop helix motif common in ?
- transcription factors (helix-basic- loop-helix)
| - cell signalling proteins that bind Ca2+ (EF-hand)
69
Greek key motif
3 anti-parallel beta strands connected by hairpins plus a 4th strand which is adjacent to the 1st + linked to the 3rd by a longer loop
70
What are greek key motifs common in?
A range of proteins
- proteases (trypsin)
- cytokines (TNF alpha)
71
What function do greek key motives have?
NO specific function
72
Coiled coil motif
Contain repeats of a 7 RESIDUE PATTERN (hxxhcxc)
73
In coiled coil motifs, resulting amphipathic alpha helices have a .....
a "stripe" of hydrophobic residues that coil around similar stripes in other helices such that hydrophilic residues project outwards
74
Examples of coiled coil motif?
Leu zippers in transcription factors e.g. c-Fos
| Structural proteins e.g. Myosins
75
Zinc finger motif
2 antiparallel beta sheets followed by 1 alpha helix , stabilised by a zinc iron
76
What can zinc finger motifs bond to?
Fe, Zn / no metal at all
77
What is metal bonding in zinc finger motifs mediated by?
Cys (in beta sheets) + His (in alpha helix)
78
Can zinc finger motifs be present frequently within the same polypeptide chain?
YES
79
Functions of zinc finger motifs?
Binding of DNA , RNA , lipid + protein substrates
80
Zinc finger motifs are common motifs in many proteins including ......
Transcription factors e.g. Kruppel-like factor 4 (KLF4)
81
Beta barrel motif
Multiple anti-parallel beta-sheets that twist + to form a closed structure
82
The first strand in a beta barrel motif is .......
H bonded to the last
83
Types of beta barrel motifs
Greek key barrel
Up-and-down barrel
Jelly roll barrel (complex)
Beta-helix barrel
84
Why are beta barrel motifs pore-forming?
Can form water channels (aquaporins)
85
Up-and-down barrel
8 anti-parallel beta-sheets connected by hairpin loops e.g. retinol-binding protein
86
Jelly roll barrel (complex)
8 beta strands arranged as 2x 4 stranded antiparallel beta sheets which wrap around a hydrophobic interface
e.g. major capsid protein P2 from bacteriophage PM2
87
Pore forming barrel
Complexes of protein subunits each with 2x 4 stranded antiparallel beta sheets
- Polar side chains form channel for hydrophilic molecules
e. g. Porin 1
88
Domains
A polypeptide chain that folds independendentLY into a stable structure WITH ITS OWN HYDROPHOBIC CORE
89
What are domains formed from?
Several simple motifs + secondary structure elements
90
How many domains can proteins have?
One to several tens of domains
91
What is each domain associated with?
A distinct biological function
92
Examples of domains
Src homology 2 (SH2) domain
-binds phospho-Tyr residues
(important in insulin signalling)
93
Tertiary structure
Overall 3D shape of the entire polypeptide
94
What are tertiary structures held together by?
1) H bonds
(between R groups)
2) Ionic bonds (ELECTROSTATIC ATTRACTION)
(between CO2- + NH3 of R groups)
3)Disulphide bridges (COVALENT CROSSLINKS)
(between cysteine -SH groups )
4)Hydrophobic interactions
(hydrophobic R groups cluster inside proteins to shield themselves from H20)
95
What do can secondary structures form form?
Long parallel fibres + sheets
96
How do long parallel fibres + sheets react with water?
Normally insoluble in H20
97
What are the functions of long parallel fibres + sheets?
Providing strength + support
98
Where are alpha keratins found?
Mammalian hair + nails
99
Where are beta keratins found?
- Invertebrates
- Silks
- Reptile scales
- Claws
- Avia feathers
- Beaks
- Claws
100
Collagen structure?
Super-helices of Gly-rich triple alpha helices (=tropocollagen) that assemble into fibrils
101
What is collagen the main protein in and what is its function?
connective tissue
| -supports , connects / separates tissues + organs
102
Is collagen abundant?
VERY (25% of total protein)
103
Collagen is .... + .....?
Strong + elastic
104
```
Bone
Cartilage
Teeth
Ligaments
Tendons
Skin
Blood vessels
Eyes (cornea + lens)
```
collagen
105
What happens when collagen goes wrong?
Ehlers Danlos Syndrome (EDS)
106
What is Ehlers Danlos Syndrome?
-A genetic connective tissue disorder
-Multiple mutations possible in multiple genes
Can affects :
Skin
Musculoskeletal
Cardiovascular
107
Alpha keratins : Hair+Nails
- Composed of coiled-coils of 2 alpha helices that assemble together into larger fibres
- Strong
- Inextensible
- Insoluble + chemically inert
- Disulphide bridges cross link coiled-coils
108
Beta keratins : Fibroin
Found in silk+spider webs
| -Layers of anti-parallel beta sheets in Ala + Gly residues
109
How do beta keratins fibroin allow close packing of beta sheets?
Small side chains interdigitate
110
How are the beta sheets joined in beta keratins fibroin?
Via amorphous stretches (confer elasticity + strength)
111
Globular proteins
Mixture of irregularly folded secondary elements to form a compact 3D shape
112
Why are globular proteins easily transported in body fluids?
Usually soluble in H20 (with inner hydrophobic core)
113
What are globular proteins a common structure for?
Enzymes
114
Examples of globular proteins?
Myoglobin
Haemoglobin
Immunoglobin
115
What is haemoglobin?
A tetramer
116
Describe haemoglobin structure?
-4 polypeptide subunits
-4 haem molecules
(haem= porphyrin + Fe2+ , O2)
117
Myoglobin
Related to haemoglobin exists as single polypeptide
118
Function of heamoglobin
- TRANSPORTS 02 from lungs to the rest of the body
| - RELEASING 02 to permit aerobic respiration to provide energy
119
Specific mutations in DNA encoding Hb genes can cause what diseases?
- Sickle cell disease
| - Thalassaemias
120
Describe carbon monoxide poisoning?
Carbon monoxide bonds haemoglobin more readily than oxygen + is released more slowly
121
What is sickle cell disease?
Disease cause by single gene defect in DNA coding region within beta globin gene
122
What type of mutation is in sickle cell disease?
Missense mutation + changes primary sequence
123
Symptoms of sickle cell disease
- Changes in RBC shape (sickle)
- RBCs rigid , become blocked in capillaries (ischaemia / organ damage / pain)
- Increased haemolysis (RBC destruction)
124
Being a carrier (heterozygous) for the sickle cell gene is protective against what?
Malaria
125
What are immunoglobulins?
Y-shaped proteins of the immune system which identifies + combats invading foreign organisms
126
Describe the structure of immunoglobulins?
- 4 chains linked by disulphide bridges
- -2 large Heavy chains
- -2 short Light chains
127
Where are the variable structures in immunoglobulins?
H + L chains
| -Form specific binding sites for non-self targets "antigens"
128
Antigen recognition by an antibody does what?
MARKS IT FOR ATTACK by other components of the immune system engaged by CONSTANT PORTIONS OF THE H CHAINS
129
Denaturation
Process in which proteins lose quaternary , tertiary + secondary structure present in their native state due to a change in environment
130
Denaturation factors
Extreme temp
Extreme pH
Organic solvent
131
What bonds are sensitive to pH and why?
iONIC BONDS
,because it disrupts the tertiary structure
-renders protein insoluble in H20 + precipitate out of solution
132
How does heat denature proteins?
Increase in temp = bonds VIBRATE + H / ionic bonds break
133
How does the extremophile thermus aquaticus grow at temps above 70c?
By producing a DNA polymerase that is stable at high temps (This is essentail for PCR)
134
List ORGANIC SOLVENTS?
Ethanol , acetone , phenol
135
How do organic solvents denature proteins?
By disrupting intra- + inter- H bonds , by forming new H bonds with protein side chains +backbone SO THE PROTEIN UNFOLDS
