Monday, August 10, 2009

A Sequence Search Study on p24 protein of HIV

A Sequence Search Study on p24 protein of HIV:


Introduction:

Human immunodeficiency virus ( HIV) is causative agent of Acquired immunodeficiency syndrome ( AIDS). HIV infects about 0.6 % of world’s population. A virus which responsible for the destruction of T- Lymphocytes of immune system cells were identified in 1984 and in 1986, it was given the name Human immunodeficiency virus ( HIV). It is a member of lentivirus. HIV having two copies of Single – Stranded RNA which enclosed by a capsid comprising the viral protein p 24. Some other proteins like Nucleocapsid proteins ( p6 and p7 ) and matrix protein ( p17) are also found in HIV. There are two strains of HIV, namely HIV- 1 and HIV -2. HIV-1 is more virulent and it infects globally. HIV- 2 is low virulent strain and is confined in West Africa.
The RNA of HIV consist of nine genes namely gag- pol, gag, env, tat, rev, nef, vif, vpr, vpu, and encoding 19 proteins. P 24 protein is translated from gag gene.
p 24 protein:
The P24 protein is core protein of HIV particles. The level of p24 protein in blood is an indicator of HIV infection progress in a patient. The sequence details of P24 protein of HIV -1 were retrieved from Protein Data Bank (Brookhaven National Laboratory). The PDB code for p24 protein is 3h47

P24 protein Sequence:

>3H47:A|PDBID|CHAIN|SEQUENCE
PIVQNLQGQMVHQCISPRTLNAWVKVVEEKAFSPEVIPMFSALSCGATPQDLNTMLNTVGGHQAAMQMLKETINEEAAEW
DRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTHNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEP
FRDYVDRFYKTLRAEQASQEVKNAATETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKARVL

Description about 3h47:

Scientific name: Human Immunodeficiency virus- type 1 ( New York-5 isolate)
Common Name:
HIV-1
Expression System: Escherichia coli

Primary structure of p24:

Number of amino acids in p24 protein is 231. Molecular weight is 25433.3 Da. Amiono acid composition of p24 protein are as follows: alanine ( 20 nos), arginine ( 11 nos), asparagine (10) aspartate ( 7), cystine (4),glutamine (15), glutamate (16), glycine (18), histidine (6),
isoleucine (15), leucine (18) , lysine ( 11) , methionine ( 10), phenylalanine (4),proline (18), serine (9), threonine (16), tryptophan (4) , tyrosine (4), valine (15). Total number of negatively charged residues (Asp + Glu) is 23 and total number of positively charged residues (Arg + Lys) is 22.

Sequence Search:

The BLAST (Basic Local Alignment Search Tool) was used to sequence search.
The Protein Blast was used to search protein database using a protein query.
The FASTA sequence of p24 protein produced following alignment.

Sequences producing significant alignments:
E-Values Score Bits
pdb|3H47|A Chain A, X-Ray Structure Of Hexameric Hiv-1 Ca >pd... 481 2e-134
gb|ACI05538.1| gag protein [Human immunodeficiency virus 1] 473 5e-132
sp|P12497.3|POL_HV1N5 RecName: Full=Gag-Pol polyprotein; AltN... 471 2e-131
gb|ABO61558.1| gag protein [Human immunodeficiency virus 1] 471 2e-131
gb|ACM46723.1| gag protein [Human immunodeficiency virus 1] >... 471 2e-131
gb|ACM46724.1| gag protein [Human immunodeficiency virus 1] 471 3e-131
gb|ACM46725.1| gag protein [Human immunodeficiency virus 1] 471 3e-131
sp|P12493.3|GAG_HV1N5 RecName: Full=Gag polyprotein; AltName:... 471 3e-131
gb|AAB60571.1| Gag polyprotein precursor [Human immunodeficie... 471 3e-131
gb|AAQ88418.1| gag protein [Human immunodeficiency virus 1] 470 4e-131
gb|AAQ88423.1| gag protein [Human immunodeficiency virus 1] 470 5e-131
gb|ACM46588.1| gag protein [Human immunodeficiency virus 1] 470 5e-131
gb|AAQ88417.1| gag protein [Human immunodeficiency virus 1] 470 5e-131
gb|AAQ88424.1| gag protein [Human immunodeficiency virus 1] 470 5e-131
gb|AAS86163.1| gag protein [Human immunodeficiency virus 1] 470 5e-131
gb|ACM46604.1| gag protein [Human immunodeficiency virus 1] 469 6e-131
gb|ACM46529.1| gag protein [Human immunodeficiency virus 1] 469 7e-131
gb|ACA49245.1| gag protein [Human immunodeficiency virus 1] 469 9e-131
gb|ABO61529.1| gag protein [Human immunodeficiency virus 1] 469 9e-131
gb|ACM46603.1| gag protein [Human immunodeficiency virus 1] 469 9e-131
gb|ACM46601.1| gag protein [Human immunodeficiency virus 1] >... 469 1e-130
gb|ABO61571.1| gag protein [Human immunodeficiency virus 1] 469 1e-130
gb|ACM46531.1| gag protein [Human immunodeficiency virus 1] 469 1e-130
gb|ABY78510.1| gag protein [Human immunodeficiency virus 1] 469 1e-130
gb|AAD03190.1| gag protein [Human immunodeficiency virus type 1] 469 1e-130
gb|ACM46477.1| gag protein [Human immunodeficiency virus 1] 469 1e-130
gb|ACM46474.1| gag protein [Human immunodeficiency virus 1] 469 1e-130
gb|AAB04036.1| gag gene product 469 1e-130
gb|AAD03191.1| gag-pol fusion polyprotein [Human immunodefici... 469 1e-130
gb|ACA49253.1| gag protein [Human immunodeficiency virus 1] 468 1e-130
gb|ABY78460.1| gag protein [Human immunodeficiency virus 1] 468 1e-130
gb|AAO63178.1| gag protein [Human immunodeficiency virus 1] 468 1e-130
gb|ACB38948.1| gag protein [Human immunodeficiency virus 1] 468 1e-130
gb|AAQ88420.1| gag protein [Human immunodeficiency virus 1] 468 1e-130
gb|ACM46383.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACM46528.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACM46447.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ABY78161.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACM46182.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACM46181.1| gag protein [Human immunodeficiency virus 1] >... 468 2e-130
gb|ABO61536.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACO50476.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|AAT80862.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACN80868.1| gag protein [Human immunodeficiency virus 1] >... 468 2e-130
gb|ACM46444.1| gag protein [Human immunodeficiency virus 1] >... 468 2e-130
gb|AAQ88414.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACM46381.1| gag protein [Human immunodeficiency virus 1] >... 468 2e-130
gb|ACM46446.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|AAQ88419.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ABQ82091.1| gag protein [Human immunodeficiency virus 1] 468 2e-130
gb|ACM46174.1| gag protein [Human immunodeficiency virus 1] >... 468 2e-130
gb|AAT80851.1| gag protein [Human immunodeficiency virus 1] 468 3e-130
gb|ACN80869.1| gag protein [Human immunodeficiency virus 1] 468 3e-130
gb|ACO50486.1| gag protein [Human immunodeficiency virus 1] 468 3e-130
gb|ACM50096.1| gag protein [Human immunodeficiency virus 1] 468 3e-130
gb|ACI05474.1| gag protein [Human immunodeficiency virus 1] 468 3e-130
gb|ACN80875.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ACM46629.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ABY78204.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ACO50554.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ABY78525.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|AAC54642.1| gag gene product 467 3e-130
gb|AAB38052.1| gag polyprotein [Human immunodeficiency virus ... 467 3e-130
gb|ACN80877.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ACM46476.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|AAX33011.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ACM46559.1| gag protein [Human immunodeficiency virus 1] 467 3e-130
gb|ACM46560.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
sp|P35963.3|POL_HV1Y2 RecName: Full=Gag-Pol polyprotein; AltN... 467 4e-130
gb|ACM46530.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ACM46631.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ACI05470.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
sp|P35962.2|GAG_HV1Y2 RecName: Full=Gag polyprotein; AltName:... 467 4e-130
gb|ACM50124.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ACM46561.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|AAB38044.1| gag polyprotein [Human immunodeficiency virus ... 467 4e-130
gb|AAC28445.1| gag protein [Human immunodeficiency virus type 1] 467 4e-130
gb|ACN80873.1| gag protein [Human immunodeficiency virus 1] >... 467 4e-130
gb|AAX32993.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ACM50017.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ACI05469.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ACM46486.1| gag protein [Human immunodeficiency virus 1] >... 467 4e-130
gb|ABY78420.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|AAK66083.1| gag polyprotein [Human immunodeficiency virus ... 467 4e-130
gb|ACO50515.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|AAQ88421.1| gag protein [Human immunodeficiency virus 1] 467 4e-130
gb|ABY78326.1| gag protein [Human immunodeficiency virus 1] 467 5e-130
gb|ABY78209.1| gag protein [Human immunodeficiency virus 1] 466 5e-130
gb|AAK66074.1| gag polyprotein [Human immunodeficiency virus ... 466 5e-130
emb|CAD26945.1| gag polyprotein [Human immunodeficiency virus... 466 5e-130
emb|CAD26947.1| gag polyprotein [Human immunodeficiency virus 1] 466 5e-130
gb|AAX33038.1| gag protein [Human immunodeficiency virus 1] 466 5e-130
gb|ABY78216.1| gag protein [Human immunodeficiency virus 1] 466 5e-130
gb|ACM46637.1| gag protein [Human immunodeficiency virus 1] 466 6e-130
gb|ABP37939.1| gag protein [Human immunodeficiency virus 1] 466 6e-130
gb|AAT80864.1| gag protein [Human immunodeficiency virus 1] 466 6e-130
gb|AAX33002.1| gag protein [Human immunodeficiency virus 1] 466 6e-130
gb|ABY78211.1| gag protein [Human immunodeficiency virus 1] 466 6e-130
dbj|BAF42561.1| Gag [Human immunodeficiency virus 1] 466 6e-130
gb|ABV00783.1| gag protein [Human immunodeficiency virus 1] 466 6e-130

Sequence Alignment:

First Alignment:

pdb|3H47|A Chain A, X-Ray Structure Of Hexameric Hiv-1 Ca >pd... 481 2e-134


Identities = 231/231 (100%), Positives = 231/231 (100%), Gaps = 0/231 (0%)

Query 1 PIVQNLQGQMVHQCISPRTLNAWVKVVEEKAFSPEVIPMFSALSCGATPQDLNTMLNTVG 60
PIVQNLQGQMVHQCISPRTLNAWVKVVEEKAFSPEVIPMFSALSCGATPQDLNTMLNTVG
Sbjct 1 PIVQNLQGQMVHQCISPRTLNAWVKVVEEKAFSPEVIPMFSALSCGATPQDLNTMLNTVG 60

Query 61 GHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTH 120
GHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTH
Sbjct 61 GHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTH 120

Query 121 NPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQE 180
NPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQE
Sbjct 121 NPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQE 180

Query 181 VKNAATETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKARVL 231
VKNAATETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKARVL
Sbjct 181 VKNAATETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKARVL 231



Last Alignment:

gb|ABV00783.1| gag protein [Human immunodeficiency virus 1] 466 6e-130

Identities = 224/231 (96%), Positives = 225/231 (97%), Gaps = 0/231 (0%)

Query 1 PIVQNLQGQMVHQCISPRTLNAWVKVVEEKAFSPEVIPMFSALSCGATPQDLNTMLNTVG 60
PIVQN+QGQMVHQ ISPRTLNAWVKVVEEKAFSPEVIPMFSALS GATPQDLNTMLNTVG
Sbjct 135 PIVQNVQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGATPQDLNTMLNTVG 194

Query 61 GHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTH 120
GHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTH
Sbjct 195 GHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTTSTLQEQIGWMTH 254

Query 121 NPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRFYKTLRAEQASQE 180
NPPIPVGEIYKRWIILGLNKIVRMYSP SILDIRQGPKEPFRDYVDRFYKTLRAEQASQE
Sbjct 255 NPPIPVGEIYKRWIILGLNKIVRMYSPASILDIRQGPKEPFRDYVDRFYKTLRAEQASQE 314

Query 181 VKNAATETLLVQNANPDCKTILKALGPGATLEEMMTACQGVGGPGHKARVL 231
VKN TETLLVQNANPDCKTILKALGP ATLEEMMTACQGVGGPGHKARVL
Sbjct 315 VKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKARVL 365


The First alignment shows 100 % of positive alignment with query. It is p24 protein whereas last alignment shows 97 % of positive alignment with our query. It is also from HIV. But it is not p24 protein. The p24 protein sequence did not produce significant alignments with any other organisms. So, It is a characteristic protein for HIV.




References:
1)Journal of Infectious Diseases 2002;186:1181-1185
2)Stephen F. Altschul, Thomas L. Madden, Alejandro A. Schäffer, Jinghui Zhang, Zheng Zhang, Webb Miller, and David J. Lipman (1997), "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs", Nucleic Acids Res. 25:3389-3402.
3)X-ray structures of the hexameric building block of the HIV capsid.Pornillos, O., Ganser-Pornillos, B.K., Kelly, B.N., Hua, Y., Whitby, F.G., Stout, C.D., Sundquist, W.I., Hill, C.P., Yeager, M.(2009) Cell(Cambridge,Mass.) 137: 1282-1292

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