Project in BioInformatics Variability of Membrane proteins of different HIV strains By Emad Nimer...
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Project in BioInformatics Variability of Membrane proteins of different HIV strains By Emad Nimer Wisam Kadry
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Transcript of Project in BioInformatics Variability of Membrane proteins of different HIV strains By Emad Nimer...
Project in BioInformatics
Variability of Membrane proteins of different HIV strains
By
Emad NimerWisam Kadry
Hiv groups & subtypes
hiv
hiv2 hiv1
O M
A J
PredominantLess easily transmittedLonger period between infection And illness
(Cameron)
(Europe)
Hiv types
Hiv1 groups
M subtypes
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
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
Methodology & Tools
Expected Results
SIG V1 V2 V3
CS FD HR1
HR2
TM CYT D
361 131 345185 370 509
510 527512 546 579 628 655 685 705 856
gp120
gp41
SIG-signal peptideV1/V2/V3-loopsCS-cleavage siteFD-fusion domain
HR1/2-heptad repeats TM-trans membrane domainCYT D-cytoplasmic domain
Results-conserved regions
Domain,residues
Explanation
37-50,280,425,124-130
CD4 binding sitesgp120
120/1,418/9 421/2 CCR5 binding sitesgp120
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 levelsof 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.
multalinSIG CD4 binding site
multalinV1/V2 loops
MEME-finding motifs4
6
9
7
10
6
3
3
8
3
8
4
4
6
9
7
10
6
3
3
8
3
8
4
4
4
6
9
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6
3
3
8
3
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4
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3
3
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4
4
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3
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| | | | | | | | | | | | | | | | | | | | | | | | | | | |
450 475 500 525 550 575 600 625 650 675 700 725 750 775 800
2D Structure Prediction of Gp160
856511
Gp41 Gp120
v3
HR1
HR2
TM Cyto
α,β C, β β,α
α βC α,β,C α,C
v1
v2
131 185 345 370 546 579 628 655685705
Conclusions 1. Conserved regions/residues have an
importantrole 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 ?
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 proteinand gp160 ?
2. Our results showed that hiv1 has 6 heptad repeats while hiv2 has only three. Is that true ? (try to use other tools).
