Project in BioInformatics
Variability of Membrane proteins
of different HIV strains
By
Emad Nimer
Wisam Kadry
Hiv groups & subtypes
hiv
Less easily transmitted
Longer period between
infection And illness
hiv2
Hiv types
hiv1
(Cameron)
O
Predominant
Hiv1 groups
M
A
M subtypes
J (Europe)
The 20 chosen strains:
hiv1: O(1 strain), M(13 strains from subtypes A,D,E,F,G,J)
hiv2(6 strains)
HIV Infection
The Membrane Protein Gp160
Gp160:
Gp120+Gp41
Project goal
explanation of regions of
conservation/variability in the gp160
protein for different hiv strains
Methodology & Tools
1. Extracting the gp160 sequences.
hiv sequence database- http://hiv-web.lanl.gov/
2. Detect conserved/variable residues.
Multiple alignment- multalin/clustw
3. Detect motifs.
MEME
4. Detect conserved 2D-structure - PSIPRED
Expected Results
gp120
SIG
gp41
1
V1
36
CS
510
FD
512
V2
131
HR1
527 546
SIG-signal peptide
V1/V2/V3-loops
CS-cleavage site
FD-fusion domain
V3
185
HR2
579
628
345
TM
655 685
370
CYT D
705
HR1/2-heptad repeats
TM-trans membrane domain
CYT D-cytoplasmic domain
856
509
Results-conserved regions
Domain,residues
Explanation
37-50,280,425,124-130 CD4 binding sites
gp120
120/1,418/9 421/2
CCR5 binding sites
gp120
88,198,241,339
Glycosylation sites gp120
511
Cleavage site
685-705
Trans membrane gp41
Conserved regions within groups
Domain,residues Explanation
1-36
signal peptide -Targeting to and
translocation across different
membranes’ cells gp120
230-340
bridging sheet :is likely includes
components of CCR5-binding site
283,370,368,472-474 CD4 binding sites gp120
512-527
Fusion domains gp41
546-579,628-655
HR1 and HR2:two heptad repeats
motifs results
706-856
Cytoplasmic domain:contains sequences
critical for CD4 degradation.
(different groups have different levels
of CD4 degradation)
Results-variable regions
Domain,residues Explanation
131-185 (V1,V2)
V1/V2 loops, part of CD4 binding
site, their variability disrupt
blocking the CD4 binding by the
antibodies. Loops have a flexible
structure(that explains the low
consensus).
345-370 (V3)
V3 loop ,includes CCR5 binding
sites.
SIG
multalin
CD4
binding site
V1/V2 loops
multalin
MEME-finding motifs
4
6
9
9
1
0
7
6
9
6
4
6
9
4
6
9
6
6
1
0
1
0
9
5
4
6
7
6
9
9
7
4
6
9
3
7
5
5
3
6
5
5
5
4
4
6
3
3
8
3
8
4
4
8
3
8
8
3
8
3
6
3
8
8
3
8
3
8
3
4
8
8
3
8
4
4
3
3
3
4
8
8
4
8
3
3
4
4
8
3
4
4
8
3
8
4
4
4
4
3
8
4
4
4
4
4
4
8
3
6
3
8
3
6
4
8
1
0
3
6
4
8
6
5
8
8
3
4
3
6
6
4
3
3
3
4
8
3
7
8
8
6
6
4
3
3
3
8
3
3
3
1
0
3
6
3
4
7
9
6
8
3
3
3
6
7
9
6
1
0
1
0
6
3
8
3
7
7
4
6
1
0
7
3
3
7
9
9
3
1
0
7
6
6
6
7
9
6
1
0
7
4
4
8
3
4
8
4
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475
500
525
550
575
600
625
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675
700
725
750
775
800
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2D Structure Prediction of Gp160
α,β
C, β
β,α
v v
1 2
131
185
α
β
C
Gp120
Gp41
α,β,C
α,C
v
3
HR
1
345 370
511 546 579 628
HR
2
T
M
655 685 705
Cyto
856
Conclusions
1.
Conserved regions/residues have an important
role in the functionality gp160 proteins,such as:
trans membrane domain (high affinity to
lymphocyte cell’s membrane),
CD4/CCR5 binding sites and glycosation sites .
2. Conserved regions within the groups attribute group
speciality such as different levels of infections :
Why hiv1 is more dominant?
• More binding sites
•Higher level of CD4 degradation (Cytoplasmic domain)
•Different pre-fusion complexes (hiv1 has 6 heptads and hiv2 has 3)
3. Variable regions are loops near binding sites ,their variability
disrupt antibodies performance.
(that is why HIV is so dangerous)
Future research
1. Investigate the variable regions V1/V2/V3,
Is mutation random ?
2. Our results showed that hiv1 has 6 heptad repeats
while hiv2 has only three.
Is that true ? (try to use other tools).
3. Include more strains to yield better sampling.
4. Investigate the conserved/variable regions of the
Gag protein.
Is there any interaction or correlation between Gag protein
and gp160 ?