3DNO

Molecular structure for the HIV-1 gp120 trimer in the CD4-bound state

Summary for 3DNO

• Entry DOI: 10.2210/pdb3dno/pdb
• Related: 1GC1 3DNL 3DNN
• EMDB information: 5018 5019 5020
• Descriptor: HIV-1 envelope glycoprotein gp120 (3 entities in total)
• Functional Keywords: hiv-1, envelope glycoprotein, immunodeficiency virus, gp120, aids, apoptosis, cleavage on pair of basic residues, envelope protein, fusion protein, host-virus interaction, lipoprotein, membrane, palmitate, viral immunoevasion, virion, viral protein
• Biological source: HIV-1 M:B_HXB2R; More
• Total number of polymer chains: 9
• Total formula weight: 96379.65

Authors

Borgnia, M.J.,Liu, J.,Bartesaghi, A.,Sapiro, G.,Subramaniam, S. (deposition date: 2008-07-02, release date: 2008-08-19, Last modification date: 2024-10-30)

Primary citation

Liu, J.,Bartesaghi, A.,Borgnia, M.J.,Sapiro, G.,Subramaniam, S.
Molecular architecture of native HIV-1 gp120 trimers.
Nature, 455:109-113, 2008

PubMed Abstract: The envelope glycoproteins (Env) of human and simian immunodeficiency viruses (HIV and SIV, respectively) mediate virus binding to the cell surface receptor CD4 on target cells to initiate infection. Env is a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120), and forms trimers on the surface of the viral membrane. Using cryo-electron tomography combined with three-dimensional image classification and averaging, we report the three-dimensional structures of trimeric Env displayed on native HIV-1 in the unliganded state, in complex with the broadly neutralizing antibody b12 and in a ternary complex with CD4 and the 17b antibody. By fitting the known crystal structures of the monomeric gp120 core in the b12- and CD4/17b-bound conformations into the density maps derived by electron tomography, we derive molecular models for the native HIV-1 gp120 trimer in unliganded and CD4-bound states. We demonstrate that CD4 binding results in a major reorganization of the Env trimer, causing an outward rotation and displacement of each gp120 monomer. This appears to be coupled with a rearrangement of the gp41 region along the central axis of the trimer, leading to closer contact between the viral and target cell membranes. Our findings elucidate the structure and conformational changes of trimeric HIV-1 gp120 relevant to antibody neutralization and attachment to target cells.

PubMed: 18668044
DOI: 10.1038/nature07159

Experimental method

ELECTRON MICROSCOPY (20 Å)