Function of HIV Env

  • HIV env gene encodes GP120 and GP41, both of which are enveople proteins for viral entry.

  • Env which binds to host receptors forms as a trimer structure on HIV particles .

  • Human antibodies mostly target HIV Env to identiy the intruders, and HIV vaccines are developed mostly containing the Env gene .

Reference

  1. Guangdi Li, Supinya Piampongsant, Nuno Rodrigues Faria, Arnout Voet, Andrea-Clemencia Pineda-Peña, Ricardo Khouri, Philippe Lemey, Anne-Mieke Vandamme, Kristof Theys. An integrated map of HIV genome-wide variation from a population perspective. Retrovirology 12, 18, doi:10.1186/s12977-015-0148-6 (2015). [PDF] [PubMed Link]
  2. Guangdi Li, HIV genome-wide diversity, interaction and coevolution. Phd thesis, Faculty of Medicine, KU Leuven, 2014 [KULeuven Link]

Sequence

(1) Reference sequence for HIV-1 Env

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

  • Fasta format: Download

  • Reference sequence:

  1       10         20         30         40         50
| | | | | |
MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT
51 60 70 80 90 100
| | | | | |
TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM
101 110 120 130 140 150
| | | | | |
VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGRMIME
151 160 170 180 190 200
| | | | | |
KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD IIPIDNDTTS YKLTSCNTSV
201 210 220 230 240 250
| | | | | |
ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT NVSTVQCTHG
251 260 270 280 290 300
| | | | | |
IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN
301 310 320 330 340 350
| | | | | |
NNTRKRIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR
351 360 370 380 390 400
| | | | | |
EQFGNNKTII FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW
401 410 420 430 440 450
| | | | | |
STEGSNNTEG SDTITLPCRI KQIINMWQKV GKAMYAPPIS GQIRCSSNIT
451 460 470 480 490 500
| | | | | |
GLLLTRDGGN SNNESEIFRP GGGDMRDNWR SELYKYKVVK IEPLGVAPTK
501 510 520 530 540 550
| | | | | |
AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ ARQLLSGIVQ
551 560 570 580 590 600
| | | | | |
QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
601 610 620 630 640 650
| | | | | |
KLICTTAVPW NASWSNKSLE QIWNHTTWME WDREINNYTS LIHSLIEESQ
651 660 670 680 690 700
| | | | | |
NQQEKNEQEL LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA
701 710 720 730 740 750
| | | | | |
VLSIVNRVRQ GYSPLSFQTH LPTPRGPDRP EGIEEEGGER DRDRSIRLVN
751 760 770 780 790 800
| | | | | |
GSLALIWDDL RSLCLFSYHR LRDLLLIVTR IVELLGRRGW EALKYWWNLL
801 810 820 830 840 850
| | | | | |
QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGACRAI RHIPRRIRQG
851 806
| |
LERILL

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

  • Strain: SIV Mac239 (ID: M33262)

  • Fasta format: Download

  • Reference sequence:

  1       10         20         30         40         50
| | | | | |
MGCLGNQLLI AILLLSVYGI YCTLYVTVFY GVPAWRNATI PLFCATKNRD
51 60 70 80 90 100
| | | | | |
TWGTTQCLPD NGDYSEVALN VTESFDAWNN TVTEQAIEDV WQLFETSIKP
101 110 120 130 140 150
| | | | | |
CVKLSPLCIT MRCNKSETDR WGLTKSITTT ASTTSTTASA KVDMVNETSS
151 160 170 180 190 200
| | | | | |
CIAQDNCTGL EQEQMISCKF NMTGLKRDKK KEYNETWYSA DLVCEQGNNT
201 210 220 230 240 250
| | | | | |
GNESRCYMNH CNTSVIQESC DKHYWDAIRF RYCAPPGYAL LRCNDTNYSG
251 260 270 280 290 300
| | | | | |
FMPKCSKVVV SSCTRMMETQ TSTWFGFNGT RAENRTYIYW HGRDNRTIIS
301 310 320 330 340 350
| | | | | |
LNKYYNLTMK CRRPGNKTVL PVTIMSGLVF HSQPINDRPK QAWCWFGGKW
351 360 370 380 390 400
| | | | | |
KDAIKEVKQT IVKHPRYTGT NNTDKINLTA PGGGDPEVTF MWTNCRGEFL
401 410 420 430 440 450
| | | | | |
YCKMNWFLNW VEDRNTANQK PKEQHKRNYV PCHIRQIINT WHKVGKNVYL
451 460 470 480 490 500
| | | | | |
PPREGDLTCN STVTSLIANI DWIDGNQTNI TMSAEVAELY RLELGDYKLV
501 510 520 530 540 550
| | | | | |
EITPIGLAPT DVKRYTTGGT SRNKRGVFVL GFLGFLATAG SAMGAASLTL
551 560 570 580 590 600
| | | | | |
TAQSRTLLAG IVQQQQQLLD VVKRQQELLR LTVWGTKNLQ TRVTAIEKYL
601 610 620 630 640 650
| | | | | |
KDQAQLNAWG CAFRQVCHTT VPWPNASLTP KWNNETWQEW ERKVDFLEEN
651 660 670 680 690 700
| | | | | |
ITALLEEAQI QQEKNMYELQ KLNSWDVFGN WFDLASWIKY IQYGVYIVVG
701 710 720 730 740 750
| | | | | |
VILLRIVIYI VQMLAKLRQG YRPVFSSPPS YFQQTHIQQD PALPTREGKE
751 760 770 780 790 800
| | | | | |
RDGGEGGGNS SWPWQIEYIH FLIRQLIRLL TWLFSNCRTL LSRVYQILQP
801 810 820 830 840 850
| | | | | |
ILQRLSATLQ RIREVLRTEL TYLQYGWSYF HEAVQAVWRS ATETLAGAWG
851 860 870 879
| | | |
DLWETLRRGG RWILAIPRRI RQGLELTLL

(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 Envar 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

Tertiary structure of HIV-1 Env

Here, we simulate a structure movie to show the dynamtic interaction between HIV-1 Env (on top) and the coreceptors on host membrane.

Lipid bilayers of extracellular membrane are shown at the bottom where nitrogen and phosphorus are indicated by blue and yellow spheres. Crystalized structure of CXCR4 coreceptor in green is placed in the center across the extracellular membrane. Lipid bilayers of membrane systems are simulated using AMBER lipid force field

Protein structures are modeled using PyMOL V1.7

  1. GP120 positions: 31-505 (PDB codes: 4JM2, 4TVP, 4NCO);
  2. GP41 positions: 518-664 (PDB codes: 4JM2, 4TVP, 4NCO);
  3. CD4 positions: 26-388, 397-458 (PDB codes: 1WIO, 2KLU).
  4. CXCR4 positions: 27-328 (PDB code: 3ODU);

Localization

(1) Coding region of Env at the HIV genome


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

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


Anti-HIV inhibitor

(1) Drug binding pocket of HIV-1 Env

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



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

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



Protein-protein interactions