Binding of gp120 of ENV oligomer to the host CD4

Stable Identifier
Reaction [binding]
Homo sapiens
Related Species
Human immunodeficiency virus 1
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CD4, located on the host cell membrane, is the main cellular receptor for the HIV protein gp120, which aids in mediating viral entry into target cells. The initial step in this cascade of events is the binding of viral gp120 protein to its host receptor, CD4. The key binding sites in CD4 for interaction with gp120 are located in the amino-terminal part of the CD4 molecule, distal to the transmembrane domain. The gp120 protein forms an oligomer (trimer) on the viral membrane with each gp120 protein containing variable domains (known as loops) and conservative domains. The V3 loop is also often obscured by gp120 glycosylation. Crystallization studies of CD4 suggest that the molecule has two immunoglobulin like domains important for the CD4/gp120 interaction, with one of the domains (D1) playing a more prominent role. Further studies suggest the Phe 43 and Arg 59 residues of CD4 play a major role in complex formation. Crystallization of gp120 shows that the polypeptide chain is folded into two major domains (an "inner" and "outer" domain with respect to the N and C termini), with the distal end of the “outer” domain containing the V3 loop. Studies of CD4 complexed with gp120 show that CD4 is bound to gp120 in a depression which is formed at the interface between the inner and outer domains. The complex itself is held together through van der Waals forces and hydrogen bonding.

Literature References
PubMed ID Title Journal Year
6096719 The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus

Greaves, MF, Beverley, PC, Weiss, RA, Crawford, DH, Clapham, PR, Dalgleish, AG

Nature 1984
9641677 Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody

Sodroski, J, Hendrickson, WA, Sweet, RW, Robinson, J, Wyatt, R, Kwong, PD

Nature 1998
2247146 Crystal structure of an HIV-binding recombinant fragment of human CD4

Xuong, NH, Porter, TG, Rosenberg, M, Arthos, J, Sweet, RW, Ryu, SE, Kwong, PD, Axel, R, Dai, XP, Truneh, A

Nature 1990
6083454 T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV

Hercend, T, Gruest, J, Champagne, E, Klatzmann, D, Gluckman, JC, Guetard, D, Montagnier, L, Chamaret, S

Nature 1984
3001934 Binding of HTLV-III/LAV to T4+ T cells by a complex of the 110K viral protein and the T4 molecule

Cort, SP, McDougal, JS, Sligh, JM, Nicholson, JK, Kennedy, MS, Mawle, A

Science 1986
2428879 Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry

Cort, SP, Cross, GD, McDougal, JS, Mawle, AC, Nicholson, JK, Kennedy, MS

J Immunol 1986
Name Identifier Synonyms
Human immunodeficiency virus infectious disease DOID:526 HIV infection
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