GAG-POL Polyprotein

HIV POL encodes the viral enzymes protease, reverse transcriptase, and integrase. The enzymes are produced as a GAG-POL precursor polyprotein, which is processed by viral protease.





Key web links:
ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB: none available
UniProt: P04585 (HIV-1 HXB2 Pol)
Chime Tutorial: not available
HIV-1/Human Protein Interaction DB: HIV-1 Pol
Los Alamos HIV structure DB: not available
EMBL: K03455 [EMBL/GenBank/DDBJ]


Isoforms:

  • GAG-POL Polyprotein (1003 amino acids)
  • p160 - GAG-POL Polyprotein


Cleavage sites:


Function:

  • Precursor for viral enzymes.
  • Mediates (with pr55Gag) the essential events in virion assembly, including binding to 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) .
  • Finally, the release of the protease from pr160GagPol triggers the virion maturation .

Localization:

  • Virion
  • Cell cytoplasm
  • Plasma membrane
  • Late endosomes/Multivesicular bodies

Additional Information:

  • Late timing of expression.
  • All of the pol gene products can be found in the capsid of the virion.
  • The Gag-Pol precursor is generated by a ribosome frameshift at the C-terminus of GAG .
  • This ribosome frameshift is triggered by a specific cis-acting RNA motif, which consists of a hepta-nucleotide sequence followed by a short stem-loop in the distal region of the GAG RNA .
  • The frequency of ribosomal frameshifting coincides with the 20:1 ratio of Gag to Gag-Pol precursors .
  • Protease cleavage does not occur efficiently, and 50% of the Reverse Transcriptase protein remain covalently associated to RNase H (p66 RT + RNase H) .
  • The completely cleaved reverse transcriptase (p51) forms a heterodimer with p66 RT .

POL Function & Host-Virus Protein Interactions:[TOP]




Interactions highlighted in the image:


  • HIV-1 Protease cleaves pol.
  • Interacts with the plasma through the phosphatidyl-inositol-4,5-bisphosphate binding domain and the myristoyl moiety.

Potential interactions (not in the image):



Genomic Location & Protein Sequence: [TOP]

HIV-1 (HXB2):

          10         20         30         40         50         60         70         80         90        100
| | | | | | | | | |
FFREDLAFLQ GKAREFSSEQ TRANSPTRRE LQVWGRDNNS PSEAGADRQG TVSFNFPQVT LWQRPLVTIK IGGQLKEALL DTGADDTVLE EMSLPGRWKP
110 120 130 140 150 160 170 180 190 200
| | | | | | | | | |
KMIGGIGGFI KVRQYDQILI EICGHKAIGT VLVGPTPVNI IGRNLLTQIG CTLNFPISPI ETVPVKLKPG MDGPKVKQWP LTEEKIKALV EICTEMEKEG
210 220 230 240 250 260 270 280 290 300
| | | | | | | | | |
KISKIGPENP YNTPVFAIKK KDSTKWRKLV DFRELNKRTQ DFWEVQLGIP HPAGLKKKKS VTVLDVGDAY FSVPLDEDFR KYTAFTIPSI NNETPGIRYQ
310 320 330 340 350 360 370 380 390 400
| | | | | | | | | |
YNVLPQGWKG SPAIFQSSMT KILEPFRKQN PDIVIYQYMD DLYVGSDLEI GQHRTKIEEL RQHLLRWGLT TPDKKHQKEP PFLWMGYELH PDKWTVQPIV
410 420 430 440 450 460 470 480 490 500
| | | | | | | | | |
LPEKDSWTVN DIQKLVGKLN WASQIYPGIK VRQLCKLLRG TKALTEVIPL TEEAELELAE NREILKEPVH GVYYDPSKDL IAEIQKQGQG QWTYQIYQEP
510 520 530 540 550 560 570 580 590 600
| | | | | | | | | |
FKNLKTGKYA RMRGAHTNDV KQLTEAVQKI TTESIVIWGK TPKFKLPIQK ETWETWWTEY WQATWIPEWE FVNTPPLVKL WYQLEKEPIV GAETFYVDGA
610 620 630 640 650 660 670 680 690 700
| | | | | | | | | |
ANRETKLGKA GYVTNRGRQK VVTLTDTTNQ KTELQAIYLA LQDSGLEVNI VTDSQYALGI IQAQPDQSES ELVNQIIEQL IKKEKVYLAW VPAHKGIGGN
710 720 730 740 750 760 770 780 790 800
| | | | | | | | | |
EQVDKLVSAG IRKVLFLDGI DKAQDEHEKY HSNWRAMASD FNLPPVVAKE IVASCDKCQL KGEAMHGQVD CSPGIWQLDC THLEGKVILV AVHVASGYIE
810 820 830 840 850 860 870 880 890 900
| | | | | | | | | |
AEVIPAETGQ ETAYFLLKLA GRWPVKTIHT DNGSNFTGAT VRAACWWAGI KQEFGIPYNP QSQGVVESMN KELKKIIGQV RDQAEHLKTA VQMAVFIHNF
910 920 930 940 950 960 970 980 990 1000
| | | | | | | | | |
KRKGGIGGYS AGERIVDIIA TDIQTKELQK QITKIQNFRV YYRDSRNPLW KGPAKLLWKG EGAVVIQDNS DIKVVPRRKA KIIRDYGKQM AGDDCVASRQ DED
[download in fasta format]

Length: 1003 amino acids
Molecular Weight: 113779 Da


Protein Domains/Folds/Motifs: [TOP]

p15- Protease (99 amino acids)
p51 - Reverse Transcriptase (440 amino acids)
p66 - RT and RNase H (560 amino acids)
p15 - RNase H (120 amino acids)
p31 - Integrase (288 amino acids)


Secondary Structure prediction:

Low Complexity Region - seg:


Antigenic Sites - EMBOSS:

Predicted Motifs: Printer-friendly version

N-glycosylation:
N-myristoylation:
Amidation:
Protein kinase C:
Casein kinase II:
Tyrosine kinase:
cAMP / cGMP kinase:
Cell attachment motif:
Asp Protease motif:
Asp Prot Retro motif:
Cysteine-rich Region:
Tryptophan-rich Region:
Zinc-finger CCHC motif:
Leucine Zipper motif:

Primary and Secondary Database Entries: [TOP]

Identifiers:



ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB/MMDB: Search for HIV-1 & POL

UniProt: P04585 (HIV-1 HXB2 Pol)
EMBL: K03455; AAB50259.1 [EMBL/GenBank/DDBJ]

MEROPS: A02.001
InterPro: IPR000477 - RNA-directed DNA polymerase (RT) family / IPR001037 - Integrase C-terminal family
IPR001584 - Integrase catalytic domain / IPR001969 - Eukaryotic/viral aspartic protease active site
IPR001995 - Retroviral Aspartic Protease family/ IPR002156 - RNase H domain
IPR003308 - Integrase N-terminal zinc-binding domain
Pfam: P04585 - POL / PF00078 - RVT / PF00665 - RVE / PF00077 - RVP / PF00075 - RNase H / PF00552 - Integrase
PF02022 - Integrase Zinc-binding
Prints: none
SCOP: SSF56672 - DNA/RNA polymerase / SSF50630 - Acid protease / SSF53098 - RNase H-like protein
SSF46919 - Integrase N-terminal Zn-binding domain / SSF50122 - Integrase C-terminal DNA-binding domain
BLOCKS: P04585
Prosite: P04585
ProtoNet: P04585
Database of Interacting Proteins: P04585
ModBase: P04585
HIV-1/Human Protein Interaction DB: HIV-1 Pol
HIV-1 Sequence Database Los Alamos HIV Sequence Database


Reviews and References: [TOP]

Cite the resource by citing the following paper:
Doherty R et al. BioAfrica's HIV-1 Proteomics Resource: Combining protein data with bioinformatics tools. Retrovirology (2005), 9;2(1):18.

1 - HIV Sequence Compendium 2000
Kuiken CL, Foley B, Hahn B, Korber B, Marx PA, McCutchan F, Mellors JW, Mullins JI, Sodroski J, Wolinksy S.
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: Compendium]
2 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
3 - Molecular Characteristics of HIV-1 Subtype C Viruses from KwaZulu-Natal, South Africa:
Implications for Vaccine and Antiretroviral Control Strategies.
Gordon M, De Oliveira T, Bishop K, Coovadia HM, Madurai L, Engelbrecht S, Janse van Rensburg E, Mosam A, Smith A, Cassol S.
Journal of Virology 77(4): 2587-2599 (2003) [pubmed: 12551997]
4 - Characterization of ribosomal frameshifting in HIV-1 Gag-Pol expression.
Jacks T, Power MD, Masiarz FR.
Nature 331: 280-283 (1988) [pubmed: 2447506]
5 - Human immunodeficiency virus type 1 gag-pol frameshifting is dependent on
mRNA secondary structure: Demonstration by expression in vivo.
Parkin NT, Chamorro M, Varmus HE.
J Virol 66: 5147-5151 (1992) [pubmed: 1321294]
6 - HIV-1 assembly, budding, and maturation.
Sundquist WI, Kräusslich HG.
Cold Spring Harb Perspect Med. 2(7):a006924 (2012) [pubmed: 22762019]
7 - Autoprocessing of HIV-1 protease is tightly coupled to protein folding.
Louis JM, Clore GM, Gronenborn AM.
Nat Struct Biol. 6(9):868-75 (1999) [pubmed: 10467100]
8 - Association of RNA helicase a with human immunodeficiency virus type 1 particles.
Roy BB, Hu J, Guo X, Russell RS, Guo F, Kleiman L, Liang C.
J Biol Chem. 281(18):12625-35 (2006) [pubmed: 16527808]
9 - The host protein Staufen1 interacts with the Pr55Gag zinc fingers and regulates HIV-1 assembly via its N-terminus.
Chatel-Chaix L, Boulay K, Mouland AJ, Desgroseillers L.
Retrovirology 5:41 (2008) [pubmed: 18498651]
10 - ESCRT-II's involvement in HIV-1 genomic RNA trafficking and assembly.
Ghoujal B, Milev MP, Ajamian L, Abel K, Mouland AJ.
Biol Cell 104(12):706-21 (2012) [pubmed: 22978549]
11 - Basic residues in the nucleocapsid domain of Gag are required for interaction of HIV-1 gag with ABCE1 (HP68), a cellular protein important for HIV-1 capsid assembly.
Lingappa JR, Dooher JE, Newman MA, Kiser PK, Klein KC.
J Biol Chem. 281(7):3773-84 (2006) [pubmed: 16275648]
12 - Maintenance of the Gag/Gag-Pol ratio is important for human immunodeficiency virus type 1 RNA dimerization and viral infectivity.
Shehu-Xhilaga M, Crowe SM, Mak J.
J Virol. 75(4):1834-41 (2001) [pubmed: 11160682]
13 - Solution structural dynamics of HIV-1 reverse transcriptase heterodimer.
Seckler JM, Howard KJ, Barkley MD, Wintrode PL.
Biochemistry 48(32):7646-55 (2009) [pubmed: 19594135]



Thanks to ViralZone at the Swiss Institute of Bioinformatics (SIB) for allowing the use of their images on bioafrica.net.
Page last updated by Megan Druce, Paula Sommer and Tulio de Oliveira (UKZN/Africa Centre) & Philippe Le Mercier, Chantal Hulo and Patrick Masson (SIB/ViralZone).