Structure determination of an anti-HIV-1 Fab 447-52D–peptide complex from an epitaxially twinned data set
- Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 (United States)
- Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 (United States)
- New York VA Medical Center and New York University School of Medicine, New York, New York 10010 (United States)
Separation of two individual lattices within an epitaxially twinned data set allowed the crystal structure of the V3-specific neutralizing antibody 447-52D in complex with a V3 peptide (UG1033) to be determined. The structure confirms that the neutralization breadth of Fab 447-52D is likely to be attributable to the extensive focus on main-chain hydrogen-bond interactions with the peptide that permit the recognition of a range of V3 sequences. Although antibodies against the third variable loop (V3) of the HIV-1 viral envelope glycoprotein are among the first neutralizing antibodies to be detected in infected individuals, they are normally restricted in their specificity. X-ray crystallographic studies of V3-specific antibodies have contributed to a more thorough understanding of recognition of this epitope and of conserved features in the V3 loop that could potentially aid in the design of a multi-component vaccine. The human antibody 447-52D exhibits relatively broad neutralization of primary viral isolates compared with other V3-loop antibodies. A crystal structure of Fab 447-52D in complex with a V3 peptide (UG1033) was determined at 2.1 Å resolution. The structure was determined using an epitaxially twinned data set and in-house programs to detect and remove overlapping reflections. Although the processed data have lower than desired completeness and slightly higher than normal R values for the resolution, good-quality electron-density maps were obtained that enabled structure determination. The structure revealed an extended CDR H3 loop that forms a β-sheet with the peptide, with the predominant contacts being main-chain hydrogen bonds. The V3 peptide and Fab show high structural homology with the previously reported structures of other Fab 447-52D complexes, reinforcing the idea that the V3 loop may adopt a small set of conserved structures, particularly around the crown of the β-hairpin.
- OSTI ID:
- 22351168
- Journal Information:
- Acta Crystallographica. Section D: Biological Crystallography, Vol. 64, Issue Pt 7; Other Information: PMCID: PMC2631122; PMID: 18566514; PUBLISHER-ID: ea5083; OAI: oai:pubmedcentral.nih.gov:2631122; Copyright (c) International Union of Crystallography 2008; Country of input: International Atomic Energy Agency (IAEA); ISSN 0907-4449
- Country of Publication:
- Denmark
- Language:
- English
Similar Records
Functional and Structural Characterization of Human V3-Specific Monoclonal Antibody 2424 with Neutralizing Activity against HIV-1 JRFL
Structure of Antibody F425-B4e8 in Complex With a V3 Peptide Reveals a New Binding Mode for Hiv-1 Neutralization