3H00
Structure of the C-terminal Domain of a Putative HIV-1 gp41 Fusion Intermediate
Summary for 3H00
| Entry DOI | 10.2210/pdb3h00/pdb |
| Related | 3GWO 3H01 |
| Descriptor | Envelope glycoprotein gp160 (2 entities in total) |
| Functional Keywords | viral membrane fusion, hiv-1, gp41, envelope protein, neutralizing antibodies, aids, apoptosis, cell membrane, cleavage on pair of basic residues, disulfide bond, fusion protein, glycoprotein, host-virus interaction, lipoprotein, membrane, palmitate, transmembrane, viral immunoevasion, virion, viral protein |
| Biological source | Human immunodeficiency virus type 1 lw12.3 isolate (HIV-1) |
| Cellular location | Transmembrane protein gp41: Virion membrane; Single-pass type I membrane protein. Surface protein gp120: Virion membrane; Peripheral membrane protein: Q70626 |
| Total number of polymer chains | 4 |
| Total formula weight | 19184.62 |
| Authors | |
| Primary citation | Liu, J.,Deng, Y.,Li, Q.,Dey, A.K.,Moore, J.P.,Lu, M. Role of a putative gp41 dimerization domain in human immunodeficiency virus type 1 membrane fusion. J.Virol., 84:201-209, 2010 Cited by PubMed Abstract: The entry of human immunodeficiency virus type 1 (HIV-1) into a target cell entails a series of conformational changes in the gp41 transmembrane glycoprotein that mediates the fusion of the viral and target cell membranes. A trimer-of-hairpins structure formed by the association of two heptad repeat (HR) regions of the gp41 ectodomain has been implicated in a late step of the fusion pathway. Earlier native and intermediate states of the protein are postulated to mediate the antiviral activity of the fusion inhibitor enfuvirtide and of broadly neutralizing monoclonal antibodies (NAbs), but the details of these structures remain unknown. Here, we report the identification and crystal structure of a dimerization domain in the C-terminal ectodomain of gp41 (residues 630 to 683, or C54). Two C54 monomers associate to form an asymmetric, antiparallel coiled coil with two distinct C-terminal alpha-helical overhangs. This dimer structure is conferred largely by interactions within a central core that corresponds to the sequence of enfuvirtide. The mutagenic alteration of the dimer interface severely impairs the infectivity of Env-pseudotyped viruses. Moreover, the C54 structure binds tightly to both the 2F5 and 4E10 NAbs and likely represents a potential intermediate conformation of gp41. These results should enhance our understanding of the molecular basis of the gp41 fusogenic structural transitions and thereby guide rational, structure-based efforts to design new fusion inhibitors and vaccine candidates intended to induce broadly neutralizing antibodies. PubMed: 19846514DOI: 10.1128/JVI.01558-09 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.2 Å) |
Structure validation
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