Structure determination of an anti-HIV-1 Fab 447-52D-peptide complex from an epitaxially twinned data set.
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 angstroms 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 beta-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 beta-hairpin.
Dhillon
Amandeep K
AK
Department of Immunology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Stanfield
Robyn L
RL
Gorny
Miroslaw K
MK
Williams
Constance
C
Zolla-Pazner
Susan
S
Wilson
Ian A
IA
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D015699:HIV Envelope Protein gp120 / Q000737:chemistry* / Q000276:immunology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry / Q000276:immunology
D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; C514793:gp120 protein, Human immunodeficiency virus 1