3f58
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IGG1 FAB FRAGMENT (58.2) COMPLEX WITH 12-RESIDUE CYCLIC PEPTIDE (INCLUDING RESIDUES 315-324 OF HIV-1 GP120 (MN ISOLATE); H315S MUTATION
OverviewOverview
BACKGROUND: The third hypervariable (V3) loop of HIV-1 gp120 has been, termed the principal neutralizing determinant (PND) of the virus and is, involved in many aspects of virus infectivity. The V3 loop is required for, viral entry into the cell via membrane fusion and is believed to interact, with cell surface chemokine receptors on T cells and macrophages. Sequence, changes in V3 can affect chemokine receptor usage, and can, therefore, modulate which types of cells are infected. Antibodies raised against, peptides with V3 sequences can neutralize laboratory-adapted strains of, the virus and inhibit syncytia formation. Fab fragments of these, neutralizing antibodies in complex with V3 loop peptides have been studied, by X-ray crystallography to determine the conformation of the V3 loop., RESULTS: We have determined three crystal structures of Fab 58.2, a, broadly neutralizing antibody, in complex with one linear and two cyclic, peptides the amino acid sequence of which comes from the MN isolate of the, gp120 V3 loop. Although the peptide conformations are very similar for the, linear and cyclic forms, they differ from that seen for the identical, peptide bound to a different broadly neutralizing antibody, Fab 59.1, and, for a similar peptide bound to the MN-specific Fab 50.1. The, conformational difference in the peptide is localized around residues, Gly-Pro-Gly-Arg, which are highly conserved in different HIV-1 isolates, and are predicted to adopt a type II beta turn. CONCLUSIONS: The V3 loop, can adopt at least two different conformations for the highly conserved, Gly-Pro-Gly-Arg sequence at the tip of the loop. Thus, the HIV-1 V3 loop, has some inherent conformational flexibility that may relate to its, biological function.
About this StructureAbout this Structure
3F58 is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.
ReferenceReference
Dual conformations for the HIV-1 gp120 V3 loop in complexes with different neutralizing fabs., Stanfield R, Cabezas E, Satterthwait A, Stura E, Profy A, Wilson I, Structure. 1999 Feb 15;7(2):131-42. PMID:10368281
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