Function of HIV Gag

  • HIV Gag is a structural protein encoded by the gag gene, which provides the basic infrastructure of HIV particles [1].

  • Gag in the plasma membrane can recruit host factors (e.g. TIP47) into nascent HIV particles [2].

  • Many inhibitors have been developed to target drug binding sites in HIV-1 Gag [3].

Reference

  1. Bell, N. M. & Lever, A. M. HIV Gag polyprotein: processing and early viral particle assembly. Trends in microbiology 21, 136-144, doi:10.1016/j.tim.2012.11.006 (2013). [PubMed Link]
  2. Waheed, A. A. & Freed, E. O. HIV type 1 Gag as a target for antiviral therapy. AIDS research and human retroviruses 28, 54-75, doi:10.1089/AID.2011.0230 (2012). [PubMed Link]
  3. Guangdi Li, Jens Verheyen, Soo-Yon Rhee, Arnout Voet, Anne-Mieke Vandamme, Kristof Theys. Functional conservation of HIV-1 Gag: implications for rational drug design. Retrovirology. 10:126. doi: 10.1186/1742-4690-10-126 (2013). [PubMed Link]

Sequence

(1) Reference sequence for HIV-1 Gag

  • Strain: HIV-1 subtype B HXB2 (ID: K03455)

  • Fasta format: Download

  • Reference sequence:

  1       10         20         30         40         50
| | | | | |
MGARASVLSG GELDRWEKIR LRPGGKKKYK LKHIVWASRE LERFAVNPGL
51 60 70 80 90 100
| | | | | |
LETSEGCRQI LGQLQPSLQT GSEELRSLYN TVATLYCVHQ RIEIKDTKEA
101 110 120 130 140 150
| | | | | |
LDKIEEEQNK SKKKAQQAAA DTGHSNQVSQ NYPIVQNIQG QMVHQAISPR
151 160 170 180 190 200
| | | | | |
TLNAWVKVVE EKAFSPEVIP MFSALSEGAT PQDLNTMLNT VGGHQAAMQM
201 210 220 230 240 250
| | | | | |
LKETINEEAA EWDRVHPVHA GPIAPGQMRE PRGSDIAGTT STLQEQIGWM
251 260 270 280 290 300
| | | | | |
TNNPPIPVGE IYKRWIILGL NKIVRMYSPT SILDIRQGPK EPFRDYVDRF
301 310 320 330 340 350
| | | | | |
YKTLRAEQAS QEVKNWMTET LLVQNANPDC KTILKALGPA ATLEEMMTAC
351 360 370 380 390 400
| | | | | |
QGVGGPGHKA RVLAEAMSQV TNSATIMMQR GNFRNQRKIV KCFNCGKEGH
401 410 420 430 440 450
| | | | | |
TARNCRAPRK KGCWKCGKEG HQMKDCTERQ ANFLGKIWPS YKGRPGNFLQ
451 460 470 480 490 500
| | | | | |
SRPEPTAPPE ESFRSGVETT TPPQKQEPID KELYPLTSLR SLFGNDPSSQ

(2) Reference sequence for HIV-2 and SIV Gag

  • Strain: SIV Mac239 (ID: M33262)

  • Fasta format: Download

  • Reference sequence:

  1       10         20         30         40         50
| | | | | |
MGVRNSVLSG KKADELEKIR LRPNGKKKYM LKHVVWAANE LDRFGLAESL
51 60 70 80 90 100
| | | | | |
LENKEGCQKI LSVLAPLVPT GSENLKSLYN TVCVIWCIHA EEKVKHTEEA
101 110 120 130 140 150
| | | | | |
KQIVQRHLVV ETGTTETMPK TSRPTAPSSG RGGNYPVQQI GGNYVHLPLS
151 160 170 180 190 200
| | | | | |
PRTLNAWVKL IEEKKFGAEV VPGFQALSEG CTPYDINQML NCVGDHQAAM
201 210 220 230 240 250
| | | | | |
QIIRDIINEE AADWDLQHPQ PAPQQGQLRE PSGSDIAGTT SSVDEQIQWM
251 260 270 280 290 300
| | | | | |
YRQQNPIPVG NIYRRWIQLG LQKCVRMYNP TNILDVKQGP KEPFQSYVDR
301 310 320 330 340 350
| | | | | |
FYKSLRAEQT DAAVKNWMTQ TLLIQNANPD CKLVLKGLGV NPTLEEMLTA
351 360 370 380 390 400
| | | | | |
CQGVGGPGQK ARLMAEALKE ALAPVPIPFA AAQQRGPRKP IKCWNCGKEG
401 410 420 430 440 450
| | | | | |
HSARQCRAPR RQGCWKCGKM DHVMAKCPDR QAGFLGLGPW GKKPRNFPMA
451 460 470 480 490 500
| | | | | |
QVHQGLMPTA PPEDPAVDLL KNYMQLGKQQ REKQRESREK PYKEVTEDLL
501 510
| |
HLNSLFGGDQ

(3) Coloring scheme for above amino acids

  1. Amino acids with hydrophobic side chains (normally buried inside the protein core):

    • A - Ala - Alanine

    • I - Ile - Isoleucine

    • L - Leu - Leucine

    • M - Met - Methionine

    • V - Val - Valine

  2. Amino acids with polar uncharged side chains (may participate in hydrogen bonds):

    • N - Asn - Asparagine

    • Q - Gln - Glutamine

    • S - Ser - Serine

    • T - Thr - Threonine

  3. Amino acids with positive charged side chains:

    • H - His - Histidine

    • K - Lys - Lysine

    • R - Arg - Arginine

  4. Amino acids with negative charged side chains:

    • D - Asp - Aspartic acid

    • E - Glu - Glutamic acid

  5. Amino acids with aromatic side chains:

    • F - Phe - Phenylalanine

    • Y - Tyr - Tyrosine

    • W - Trp - Tryptophan

  6. Cysteine: C - Cys - Cysteine

  7. Glycine: G - Gly - Glycine

  8. Proline: P - Pro - Proline

Amino acid variations at HIV-1 Gag

Here, we visualize the prevalence of amino acid variations at the HIV-1 Gag from HIV-1 group M.

Protocal of our sequence collection

Detailed protocals have been described in our publication:

Guangdi Li, Jens Verheyen, Soo-Yon Rhee, Arnout Voet, Anne-Mieke Vandamme, Kristof Theys. Functional conservation of HIV-1 Gag: implications for rational drug design. Retrovirology. 10:126. doi: 10.1186/1742-4690-10-126 (2013). [PubMed Link]


Visualization of natural polymorphisms in Gag


Please cite our article:

  1. Guangdi Li, Jens Verheyen, Soo-Yon Rhee, Arnout Voet, Anne-Mieke Vandamme, Kristof Theys. Functional conservation of HIV-1 Gag: implications for rational drug design. Retrovirology. 10:126. doi: 10.1186/1742-4690-10-126 (2013). [PubMed Link]

Tertiary structure of HIV-1 Gag

Here, we provide a structure movie of Gag whose structure is modeled using PyMOL V1.7 (PDB code: Matrix, 1HIW; Capsid, 3H4E; p2, 1U57; Nucleocapsid, 1A1T; p6, 2C55). Alpha-helix and beta-strand secondary structures are demonstrated by red.

Localization

(1) Coding region of Gag at the HIV genome


(2) Localization of Gag during the HIV-1 life cycle

Here, we visualize the localization of Gag during the viral life cycle. Red stars indicate the appearance of HIV-1 Gag.


Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Gag

Here, we visualize the drug binding pocket of HIV-1 Gag



(2) List of known inhibitors targeting HIV-1 Gag

Here, we summarize the published anti-HIV inhibitors which bind to HIV-1 Gag.



Protein-protein interactions