Gag-Pol polyprotein
Details
- Name
- Gag-Pol polyprotein
- Synonyms
- Pr160Gag-Pol
- Gene Name
- gag-pol
- Organism
- HIV-1
- Amino acid sequence
>lcl|BSEQ0002517|Gag-Pol polyprotein MGARASVLSAGELDKWEKIRLRPGGKKQYRLKHIVWASRELERFAVDPGLLETSEGCRQI LGQLQPSLQTGSEELRSLYNTVATLYCVHQKIEVKDTKEALEKIEEEQNKSKKKAQQAAA DTGNSSQVSQNYPIVQNLQGQMVHQAISPRTLNAWVKVVEEKAFSPEVIPMFSALSEGAT PQDLNTMLNTVGGHQAAMQMLKETINEEAAEWDRLHPVHAGPIAPGQMREPRGSDIAGTT STLQEQIGWMTNNPPIPVGEIYKRWIILGLNKIVRMYSPTSILDIRQGPKEPFRDYVDRF YKTLRAEQASQEVKNWMTETLLVQNANPDCKTILKALGPAATLEEMMTACQGVGGPGHKA RVLAEAMSQVTNSATIMMQRGNFRNQRKTVKCFNCGKEGHIAKNCRAPRKKGCWKCGKEG HQMKDCTERQANFLREDLAFPQGKARKFSSEQTRANSPIRRERQVWRRDNNSLSEAGADR QGTVSFSFPQITLWQRPLVTIKIGGQLKEALLDTGADDTVLEEMNLPGRWKPKMIGGIGG FIKVRQYDQIPIEICGHKAIGTVLVGPTPVNIIGRNLLTQIGCTLNFPISPIETVPVKLK PGMDGPKVKQWPLTEEKIKALVEICTEMEKEGKISKIGPENPYNTPVFAIKKKDSTKWRK LVDFRELNKRTQDFWEVQLGIPHPAGLKKKKSVTVLDVGDAYFSVPLHEDFRKYTAFTIP SINNETPGTRYQYNVLPQGWKGSPAIFQSSMTTILEPFRKQNPDLVIYQYMDDLYVGSDL EIGQHRTKIEELRQHLLRWGFTTPDKKHQKEPPFLWMGYELHPDKWTVQPIVLPEKDSWT VNDIQKLVGKLNWASQIYAGIKVRQLCKLLRGTKALTEVIPLTEEAELELAENREILKEP VHGVYYDPSKDLIAEIQKQGQGQWTYQIYQEPFKNLKTGKYARTRGAHTNDVKQLTEAVQ KIATESIVIWGKTPKFKLPIQKETWETWWTEYWQATWIPEWEFVNTPPLVKLWYQLEKEP IIGAETFYVDGAANRETKLGKAGYVTNKGRQKVVSLTDTTNQKTELQAIYLALQDSGLEV NIVTDSQYALGIIQAQPDRSESELVSQIIEQLIKKEKVYLAWVPAHKGIGGNEQVDKLVS AGIRKVLFLDGIDKAQEEHEKYHSNWRAMASDFNLPPVVAKEIVASCDKCQLKGEAMHGQ VDCSPGIWQLDCTHLEGKVILVAVHVASGYIEAEVIPAETGQETAYFLLKLAGRWPVTTI HTDNGSNFTSATVKAACWWAGIKQEFGIPYNPQSQGVVESMNKELKKIIGQVRDQAEHLK TAVQMAVFIHNFKRKGGIGGYSAGERIVDIIATDIQTKELQKQITKIQNFRVYYRDSRDP LWKGPAKLLWKGEGAVVIQDNSDIKVVPRRKAKIIRDYGKQMAGDDCVAGRQDED
- Number of residues
- 1435
- Molecular Weight
- 161978.93
- Theoretical pI
- 9.07
- GO Classification
- Functionsaspartic-type endopeptidase activity / DNA binding / DNA-directed DNA polymerase activity / exoribonuclease H activity / lipid binding / RNA binding / RNA-directed DNA polymerase activity / RNA-DNA hybrid ribonuclease activity / structural molecule activity / zinc ion bindingProcessesDNA integration / DNA recombination / establishment of integrated proviral latency / induction by virus of host cysteine-type endopeptidase activity involved in apoptotic process / suppression by virus of host gene expression / viral entry into host cell / viral penetration into host nucleus / viral release from host cellComponentshost cell nucleus / host cell plasma membrane / host multivesicular body / viral nucleocapsid / virion membrane
- General Function
- Zinc ion binding
- Specific Function
- Gag-Pol polyprotein: Mediates, with Gag polyrotein, the essential events in virion assembly, including binding the plasma membrane, making the protein-protein interactions necessary to create spherical particles, recruiting the viral Env proteins, and packaging the genomic RNA via direct interactions with the RNA packaging sequence (Psi). Gag-Pol polyprotein may regulate its own translation, by the binding genomic RNA in the 5'-UTR. At low concentration, the polyprotein would promote translation, whereas at high concentration, the polyprotein would encapsidate genomic RNA and then shutt off translation.Matrix protein p17: Targets the polyprotein to the plasma membrane via a multipartite membrane-binding signal, that includes its myristoylated N-terminus. Matrix protein is part of the pre-integration complex. Implicated in the release from host cell mediated by Vpu. Binds to RNA.Capsid protein p24: Forms the conical core that encapsulates the genomic RNA-nucleocapsid complex in the virion. Most core are conical, with only 7% tubular. The core is constituted by capsid protein hexamer subunits. The core is disassembled soon after virion entry (By similarity). Host restriction factors such as TRIM5-alpha or TRIMCyp bind retroviral capsids and cause premature capsid disassembly, leading to blocks in reverse transcription. Capsid restriction by TRIM5 is one of the factors which restricts HIV-1 to the human species. Host PIN1 apparently facilitates the virion uncoating. On the other hand, interactions with PDZD8 or CYPA stabilize the capsid.Nucleocapsid protein p7: Encapsulates and protects viral dimeric unspliced genomic RNA (gRNA). Binds these RNAs through its zinc fingers. Acts as a nucleic acid chaperone which is involved in rearangement of nucleic acid secondary structure during gRNA retrotranscription. Also facilitates template switch leading to recombination. As part of the polyprotein, participates to gRNA dimerization, packaging, tRNA incorporation and virion assembly.Protease: Aspartyl protease that mediates proteolytic cleavages of Gag and Gag-Pol polyproteins during or shortly after the release of the virion from the plasma membrane. Cleavages take place as an ordered, step-wise cascade to yield mature proteins. This process is called maturation. Displays maximal activity during the budding process just prior to particle release from the cell. Also cleaves Nef and Vif, probably concomitantly with viral structural proteins on maturation of virus particles. Hydrolyzes host EIF4GI and PABP1 in order to shut off the capped cellular mRNA translation. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity).Reverse transcriptase/ribonuclease H: Multifunctional enzyme that converts the viral RNA genome into dsDNA in the cytoplasm, shortly after virus entry into the cell. This enzyme displays a DNA polymerase activity that can copy either DNA or RNA templates, and a ribonuclease H (RNase H) activity that cleaves the RNA strand of RNA-DNA heteroduplexes in a partially processive 3' to 5' endonucleasic mode. Conversion of viral genomic RNA into dsDNA requires many steps. A tRNA(3)-Lys binds to the primer-binding site (PBS) situated at the 5'-end of the viral RNA. RT uses the 3' end of the tRNA primer to perform a short round of RNA-dependent minus-strand DNA synthesis. The reading proceeds through the U5 region and ends after the repeated (R) region which is present at both ends of viral RNA. The portion of the RNA-DNA heteroduplex is digested by the RNase H, resulting in a ssDNA product attached to the tRNA primer. This ssDNA/tRNA hybridizes with the identical R region situated at the 3' end of viral RNA. This template exchange, known as minus-strand DNA strong stop transfer, can be either intra- or intermolecular. RT uses the 3' end of this newly synthesized short ssDNA to perform the RNA-dependent minus-strand DNA synthesis of the whole template. RNase H digests the RNA template except for two polypurine tracts (PPTs) situated at the 5'-end and near the center of the genome. It is not clear if both polymerase and RNase H activities are simultaneous. RNase H probably can proceed both in a polymerase-dependent (RNA cut into small fragments by the same RT performing DNA synthesis) and a polymerase-independent mode (cleavage of remaining RNA fragments by free RTs). Secondly, RT performs DNA-directed plus-strand DNA synthesis using the PPTs that have not been removed by RNase H as primers. PPTs and tRNA primers are then removed by RNase H. The 3' and 5' ssDNA PBS regions hybridize to form a circular dsDNA intermediate. Strand displacement synthesis by RT to the PBS and PPT ends produces a blunt ended, linear dsDNA copy of the viral genome that includes long terminal repeats (LTRs) at both ends.Integrase: Catalyzes viral DNA integration into the host chromosome, by performing a series of DNA cutting and joining reactions. This enzyme activity takes place after virion entry into a cell and reverse transcription of the RNA genome in dsDNA. The first step in the integration process is 3' processing. This step requires a complex comprising the viral genome, matrix protein, Vpr and integrase. This complex is called the pre-integration complex (PIC). The integrase protein removes 2 nucleotides from each 3' end of the viral DNA, leaving recessed CA OH's at the 3' ends. In the second step, the PIC enters cell nucleus. This process is mediated through integrase and Vpr proteins, and allows the virus to infect a non dividing cell. This ability to enter the nucleus is specific of lentiviruses, other retroviruses cannot and rely on cell division to access cell chromosomes. In the third step, termed strand transfer, the integrase protein joins the previously processed 3' ends to the 5' ends of strands of target cellular DNA at the site of integration. The 5'-ends are produced by integrase-catalyzed staggered cuts, 5 bp apart. A Y-shaped, gapped, recombination intermediate results, with the 5'-ends of the viral DNA strands and the 3' ends of target DNA strands remaining unjoined, flanking a gap of 5 bp. The last step is viral DNA integration into host chromosome. This involves host DNA repair synthesis in which the 5 bp gaps between the unjoined strands are filled in and then ligated. Since this process occurs at both cuts flanking the HIV genome, a 5 bp duplication of host DNA is produced at the ends of HIV-1 integration. Alternatively, Integrase may catalyze the excision of viral DNA just after strand transfer, this is termed disintegration.
- Pfam Domain Function
- Transmembrane Regions
- Not Available
- Cellular Location
- Host cell membrane
- Chromosome Location
- Not Available
- Locus
- Not Available
- External Identifiers
Resource Link UniProtKB ID P35963 UniProtKB Entry Name POL_HV1Y2 GenBank Gene ID M93258 - General References
- Li Y, Hui H, Burgess CJ, Price RW, Sharp PM, Hahn BH, Shaw GM: Complete nucleotide sequence, genome organization, and biological properties of human immunodeficiency virus type 1 in vivo: evidence for limited defectiveness and complementation. J Virol. 1992 Nov;66(11):6587-600. [Article]
- Vogt VM: Proteolytic processing and particle maturation. Curr Top Microbiol Immunol. 1996;214:95-131. [Article]
- Turner BG, Summers MF: Structural biology of HIV. J Mol Biol. 1999 Jan 8;285(1):1-32. [Article]
- Negroni M, Buc H: Mechanisms of retroviral recombination. Annu Rev Genet. 2001;35:275-302. [Article]
- Dunn BM, Goodenow MM, Gustchina A, Wlodawer A: Retroviral proteases. Genome Biol. 2002;3(4):REVIEWS3006. Epub 2002 Mar 26. [Article]
- Scarlata S, Carter C: Role of HIV-1 Gag domains in viral assembly. Biochim Biophys Acta. 2003 Jul 11;1614(1):62-72. [Article]
- Cai M, Zheng R, Caffrey M, Craigie R, Clore GM, Gronenborn AM: Solution structure of the N-terminal zinc binding domain of HIV-1 integrase. Nat Struct Biol. 1997 Jul;4(7):567-77. [Article]
- Amarasinghe GK, De Guzman RN, Turner RB, Chancellor KJ, Wu ZR, Summers MF: NMR structure of the HIV-1 nucleocapsid protein bound to stem-loop SL2 of the psi-RNA packaging signal. Implications for genome recognition. J Mol Biol. 2000 Aug 11;301(2):491-511. [Article]
- King NM, Melnick L, Prabu-Jeyabalan M, Nalivaika EA, Yang SS, Gao Y, Nie X, Zepp C, Heefner DL, Schiffer CA: Lack of synergy for inhibitors targeting a multi-drug-resistant HIV-1 protease. Protein Sci. 2002 Feb;11(2):418-29. [Article]
- Surleraux DL, Tahri A, Verschueren WG, Pille GM, de Kock HA, Jonckers TH, Peeters A, De Meyer S, Azijn H, Pauwels R, de Bethune MP, King NM, Prabu-Jeyabalan M, Schiffer CA, Wigerinck PB: Discovery and selection of TMC114, a next generation HIV-1 protease inhibitor. J Med Chem. 2005 Mar 24;48(6):1813-22. [Article]