Crystal structures of human immunodeficiency virus type 1 (HIV-1) neutralizing antibody 2219 in complex with three different V3 peptides reveal a new binding mode for HIV-1 cross-reactivity.
Human monoclonal antibody 2219 is a neutralizing antibody isolated from a human immunodeficiency virus type 1-infected individual. 2219 was originally selected for binding to a V3 fusion protein and can neutralize primary isolates from subtypes B, A, and F. Thus, 2219 represents a cross-reactive, human anti-V3 antibody. Fab 2219 binds to one face of the variable V3 beta-hairpin, primarily contacting conserved residues on the N-terminal beta-strand of V3, leaving the V3 crown or tip largely accessible. Three V3/2219 complexes reveal the antibody-bound conformations for both the N- and C-terminal regions that flank the V3 crown and illustrate how twisting of the V3 loop alters the relative dispositions and pairing of the amino acids in the adjacent V3 beta-strands and how the antibody can accommodate V3 loops with different sequences.
Stanfield
Robyn L
RL
Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA. robyn@scripps.edu
Gorny
Miroslaw K
MK
Zolla-Pazner
Susan
S
Wilson
Ian A
IA
D000936:Antigen-Antibody Complex / Q000737:chemistry*; D003429:Cross Reactions / Q000276:immunology*; D003460:Crystallization; D018360:Crystallography, X-Ray; D000939:Epitopes; D015483:HIV Antibodies / Q000737:chemistry*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry*; D011487:Protein Conformation; D017433:Protein Structure, Secondary
D000936:Antigen-Antibody Complex; D000939:Epitopes; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments