gp120 - ENV Glycoprotein 120

HIV gp120 acts as a receptor on the surface of the viral particle, and binds to CD4 and secondary receptors on macrophages and T lymphocytes





PDB-1GC1: Envelope protein complex with HIV-1 gp120 [clone HXB2 with K403E mutation] (pink ribbon), CD4 (yellow ribbon), neutralizing antibody 17B light chain (blue ribbon) and neutralizing antibody 17B heavy chain (green ribbon)  - produced using SwissModel/SPDBV/POVray
[animated gif: 320x240 ]
ViralZone:HIV-1
PDB: 1GC1 (HIV-1 HXB2 gp120 complex)
SwissProt: P04578 (HIV-1 HXB2 ENV)
Chime Tutorial: Online Macromolecular Museum
Los Alamos HIV structure DB: HIV ENV
EMBL: K03455 [EMBL/GenBank/DDBJ]
BioAfrica: Env Protein Data Mining Tool


Isoforms:

  • gp120 - exterior membrane glycoprotein (481 amino acids)

Localization:

  • Cell plasma membrane
  • Virion envelope

Function:

  • Virion attachment and entry
  • gp120 interacts with the CD4 receptor and chemokine co-receptors (Ref. #3)
  • gp120 is non-covalently bound to gp41, which transverses the lipid bilayer


Additional Information:

  • The gp120-gp41 complex exists as a trimer on the surface of infected cells and the virion
  • gp120 has 9 intrachain disulfide bonds (Ref. #4)
  • gp120 has 5 hypervariable regions (V1 through V5)

Genomic Location: [TOP]

Reference Sequences:

HIV-1 (HXB2):

          10         20         30         40         50         60         70
| | | | | | |
TEKLWVTVYY GVPVWKEATT TLFCASDAKA YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM
80 90 100 110 120 130 140
| | | | | | |
VEQMHEDIIS LWDQSLKPCV KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSIRGKVQ
150 160 170 180 190 200 210
| | | | | | |
KEYAFFYKLD IIPIDNDTTS YKLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT
220 230 240 250 260 270 280
| | | | | | |
NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN NNTRKRIRIQ
290 300 310 320 330 340 350
| | | | | | |
RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR EQFGNNKTII FKQSSGGDPE IVTHSFNCGG
360 370 380 390 400 410 420
| | | | | | |
EFFYCNSTQL FNSTWFNSTW STEGSNNTEG SDTITLPCRI KQIINMWQKV GKAMYAPPIS GQIRCSSNIT
430 440 450 460 470 480
| | | | | |
GLLLTRDGGN SNNESEIFRP GGGDMRDNWR SELYKYKVVK IEPLGVAPTK AKRRVVQREK R
[download in fasta format]

Length: 481 amino acids (residues 31 - 511)
Molecular Weight: 53922 Da
Theoretical pI: 9.05


Protein Domains/Folds/Motifs: [TOP]

InterPro signature for Envelope glycoprotein GP120 - IPR000777


Hypervariable regions (V1 through V5):

V1 variable loop:


V2 variable loop:


V3 variable loop:

  • is not involved in CD4 binding, but is important for determining the preferential tropism for either T lymphocytes or primary macrophages (Ref. #5)
  • interacts with CXCR4 and CCR5 chemokine receptors (Ref. #6 & #7)
  • is the primary target for neutralizing antibodies that block HIV-1 infectivity (Ref. #8)

V4 variable loop:


V5 variable loop:


Highly conserved intrachain disulfide bonds (Ref. #4):

(Cys54 - Cys74)
(Cys119 - Cys205)
(Cys126 - Cys196)
(Cys131 - Cys157)
(Cys218 - Cys247)
(Cys228 - Cys239)
(Cys296 - Cys331)
(Cys378 - Cys445)
(Cys385 - Cys418)


Secondary Structure Prediction:

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:





Protein-Protein Interactions: [TOP]

  • gp120 interacts with DC-SIGN, which is expressed on the surface of dendritic cells (Ref. #9)
  • DC-SIGN facilitates mucosal transmission by transporting HIV to lymphoid tissue


Primary and Secondary Database Entries: [TOP]

Identifiers:

ViralZone: HIV-1
PDB/MMDB: Search for HIV-1 & gp120

SwissProt: P04578 (HIV-1 HXB2 ENV)
EMBL: K03455; AAB50262.1 [EMBL/GenBank/DDBJ]

PIR: UNKNOWN
HIV: K03455; UNKNOWN$HXB2
InterPro: IPR000777 - gp120 family
Pfam: PF00516 - gp120 family
Prints: none
ProDom: PD597348 (1 - 52) / PD551838 (5 - 164) / PD553839 (52 - 102) / PD000124 (53 - 142)
PD000193 (53 - 103) / PD529973 (55 - 102) / PD591903 (98 - 127) / PD579607 (128 - 163)
PD499504 (128 - 157) / PD000123 (148 - 173) / PD000124 (165 - 462) / PD614419 (300 - 361)
PD561449 (338 - 461)/ PD527975 (373 - 462) / PD598762 (463 - 481)
SCOP: SSF56502 - gp120 core
BLOCKS: P04578
Prosite: P04578
ProtoNet: P04578
ProtoMap: P04578
PRESAGE: P04578
Database of Interacting Proteins: P04578
ModBase: P04578
Swiss-2DPAGE: 2D gel

BioAfrica Tools:
- Env Protein Data Mining Tool provides real-time analysis of HIV-1 Env isolates
- HIV Structure BLAST searches for similar HIV sequences that have known structures
- HIV Proteomics Resource contains protein sequence and structure analysis tools

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 1998
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 - Structure of the Core of the HIV-1 gp120 Exterior Envelope Glycoprotein
Wyatt R, Kwong PD, Hendrickson WA, Sodroski. JG
Theoretical Biol. & Biophys. Group, Los Alamos Nat Lab, LA-UR 01-3860 [Read it online: SODROSKI]
3 - 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]
4 - Retroviruses
Coffin JM, Hughes SH, Varmus HE.
CD-ROM ed. (2002) Cold Spring Harbor Laboratory Press [Read it online: NCBI Bookshelf]
5 - The envelope glycoprotein of the human immunodeficiency virus binds to the
immunoglobulin-like domain of CD4.
Landau NR, Warton M, Littman DR.
Nature 334(6178): 159-162 (1988) [pubmed: 88261570]
6 - Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and
a neutralizing human antibody.
Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA.
Nature 393(6686): 648-659 [pubmed: 98303379]
7 - Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1.
Hwang SS, Boyle TJ, Lyerly HK, Cullen BR.
Science 253: 71-74 (1991) [pubmed: 1905842]
8 - HIV-1 entry cofactor: Functional cDNA cloning of a seven-transmembrane,
G protein-coupled receptor.
Feng Y, Broder CC, Kennedy PE.
Science 272: 872-877 (1996) [pubmed: 8629022]
9 - Identification of a major co-receptor for primary isolates of HIV-1.
Deng H, Liu R, Ellmeier W.
Nature 381: 661-666 (1996) [pubmed: 8649511]
10 - Human immunodeficiency virus type 1 neutralization epitope with conserved architecture
elicits early type-specific antibodies in experimentally infected chimpanzees.
Goudsmit J, Debouck C, Meloen RH.
Proc Natl Acad Sci USA 85: 4478-4482 (1988) [pubmed: 2454471]
11 - DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells.
Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS, KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y.
Cell 100: 587-97 (2000) [pubmed: 10721995]
12 - [Glycosylation of gp120] Mass spectrometric characterization of the glycosylation pattern of
HIV-gp120 expressed in CHO cells.
Zhu X, Borchers C, Bienstock RJ, Tomer KB.
Biochemistry 39(37): 11194-11204 (2000) [pubmed: 10985765]



Page last updated by Tulio de Oliveira.