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

Key web links:
ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB: 1GC1 (HIV-1 HXB2 gp120 complex)
UniProt: P04578 (HIV-1 HXB2 ENV)
Chime Tutorial: Online Macromolecular Museum
HIV-1/Human Protein Interaction DB: HIV-1 Env
Los Alamos HIV structure DB: HIV ENV
EMBL: K03455 [EMBL/GenBank/DDBJ]


  • gp120 - exterior membrane glycoprotein (481 amino acids)


  • Virion attachment and entry.
  • Gp120 interacts with the CD4 attachment receptor and chemokine co-receptors, CCR5 and CXCR4, for attachment and entry into the host cell .
  • Gp120 is non-covalently bound to gp41 , which transverses the lipid bilayer.


  • Cell plasma membrane
  • Virion envelope

Additional Information:

  • Late timing of expression.
  • The gp120-gp41 complex exists as a trimer on the surface of infected cells and the virion.
  • Gp120 has 9 intrachain disulfide bonds .
  • Gp120 has 5 hypervariable regions (V1 through V5).

Gp120 Function & Host-Virus Protein Interactions:[TOP]

Interactions highlighted in the image:

Potential interactions (not in the image):

Genomic Location & Protein Sequence: [TOP]

HIV-1 (HXB2):

          10         20         30         40         50         60         70         80         90        100
| | | | | | | | | |
110 120 130 140 150 160 170 180 190 200
| | | | | | | | | |
210 220 230 240 250 260 270 280 290 300
| | | | | | | | | |
310 320 330 340 350 360 370 380 390 400
| | | | | | | | | |
410 420 430 440 450 460 470 480
| | | | | | | |
[download in fasta format]

Length: 481 amino acids (residues 31 - 511). Please notice that the gp120 excludes the first 30 amino acids, which are cleaved from the signal peptide, which may change numbering position. For example the envelope Cys119 - Cys 205 disulfide bond are seen on position Cys89 and Cys 175 (marked in bold and underlined).
Molecular Weight: 53922 Da
Theoretical pI: 9.05
Position relative to Env protein: 1 - 511

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 .
  • Interacts with CXCR4 and CCR5 chemokine receptors .
  • Is the primary target for neutralizing antibodies that block HIV-1 infectivity .

V4 variable loop:

V5 variable loop:

Highly conserved intrachain disulfide bonds:

(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

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:

HIV Antiretrovirals and Drug Resistance Mutations: [TOP]

See Stanford University HIV Drug Resistance Database, which contains information different HIV-1 subtypes and CRFs 01 and 02

See a recent review on HIV-1 drug resistance and subtypes, with special focus on HIV-1 subtype C, the most prevalent HIV-1 strain in the world

See ViralZone HIV Drug Pages

Mechanism of Action:

Viral entry describes a complex process that involves various steps, including the fusion of the viral membrane to the host cellular membrane.
Currently, there is only one fusion inhibitor that has been approved for HIV treatment, Enfuviritide.
This 36 amino acid polypeptide binds to the haptad repeat (HR) regions of the gp41 viral protein and engages in a coil-coil interaction.
This interaction prevents the virus particle from attaching to the host cell membrane and thus, prevents the entry and infection of HIV.

Drug Resistance Mutations:

Fusion Inhibitor:
Position Mutation Additional Information Drugs Affected Reference
G36 D, E, V, S G36D/E mutations are associated with a large decrease in Enfuviritide susceptibility (>10 fold). Enfuviritide
I37 V Enfuviritide
V38 E, A, M, G V38E/A mutations are associated with a large decrease in Enfuviritide susceptibility (>10 fold). Enfuviritide
Q40 H Mutation is associated with a large decrease in Enfuviritide susceptibility (>10 fold). Enfuviritide
N42 T, S N42S occurs in ~15% of viruses from Enfuviritide-naive patients and does not decrease drug susceptibility. Enfuviritide
N43 D, K, S N43D mutation is associated with a large decrease in Enfuviritide susceptibility (>10 fold). Enfuviritide
L44 M Enfuviritide
L45 M Enfuviritide
Primary and Secondary Database Entries: [TOP]


ViralZone: HIV-1, HIV replication cycle, HIV resource
PDB/MMDB: Search for HIV-1 & gp120

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

InterPro: IPR000777 - gp120 family
Pfam: PF00516 - gp120 family
Prints: none
SCOP: SSF56502 - gp120 core
BLOCKS: P04578
Prosite: P04578
ProtoNet: P04578
Database of Interacting Proteins: P04578
ModBase: P04578
HIV-1/Human Protein Interaction DB: HIV-1 Env
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 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: 3260352]
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 (1998) [pubmed: 9641677]
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]
13 - Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study.
Shepherd JC1, Jacobson LP, Qiao W, Jamieson BD, Phair JP, Piazza P, Quinn TC, Margolick JB.
J Infect Dis. 198(8):1104-12 (2008) [pubmed: 18783316]
14 - Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule.
McDougal JS, Kennedy MS, Sligh JM, Cort SP, Mawle A, Nicholson JK.
Science 231(4736):382-5 (1986) [pubmed: 3001934]
15 - CD4-induced interaction of primary HIV-1 gp120 glycoproteins with the chemokine receptor CCR-5.
Wu L, Gerard NP, Wyatt R, Choe H, Parolin C, Ruffing N, Borsetti A, Cardoso AA, Desjardin E, Newman W, Gerard C, Sodroski J.
Nature 384(6605):179-83 (1996) [pubmed: 8906795]
16 - Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120.
Curtis BM, Scharnowske S, Watson AJ.
Proc Natl Acad Sci U S A. 89(17):8356-60 (1992) [pubmed: 1518869]
17 - Human immunodeficiency virus (HIV) envelope binds to CXCR4 independently of CD4, and binding can be enhanced by interaction with soluble CD4 or by HIV envelope deglycosylation.
Bandres JC, Wang QF, O'Leary J, Baleaux F, Amara A, Hoxie JA, Zolla-Pazner S, Gorny MK.
J Virol. 72(3):2500-4 (1998) [pubmed: 9499113]
18 - Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update.
Bennett DE, Camacho RJ, Otelea D, Kuritzkes DR, Fleury H, Kiuchi M, Heneine W, Kantor R, Jordan MR, Schapiro JM, Vandamme AM, Sandstrom P, Boucher CA, van de Vijver D, Rhee SY, Liu TF, Pillay D, Shafer RW.
PLoS One 4(3):e4724 (2009) [pubmed: 19266092]
19 - Characterization of envelope glycoprotein gp41 genotype and phenotypic susceptibility to enfuvirtide at baseline and on treatment in the phase III clinical trials TORO-1 and TORO-2.
Melby T, Sista P, DeMasi R, Kirkland T, Roberts N, Salgo M, Heilek-Snyder G, Cammack N, Matthews TJ, Greenberg ML.
AIDS Res Hum Retroviruses 22(5):375-85 (2006) [pubmed: 16706613]

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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).