Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope

• DOI: 10.1128/jvi.78.19.10724-10737.2004
• Publication Date: 2004-09-14T20:48:09Z
• Authors: Gilad Ofek; Min Tang; Anna Sambor; Hermann Katinger; John R. Mascola; Richard Wyatt; Peter D. Kwong
• Keywords: Ectodomain

The membrane-proximal region of the ectodomain gp41 envelope glycoprotein human immunodeficiency virus type 1 (HIV-1) is target three five broadly neutralizing anti-HIV-1 antibodies thus far isolated. We have determined crystal structures antigen-binding fragment for one these antibodies, 2F5, in complex with 7-mer, 11-mer, and 17-mer peptides region, at 2.0-, 2.1-, 2.2-A resolutions, respectively. reveal an extended conformation, which stretches over 30 A length. Contacts are made complementarity-determining regions antibody as well nonpolymorphic regions. Only exclusive charged face epitope bound by while nonbound face, hydrophobic, may be hidden due to occlusion other portions ectodomain. that 2F5 uniquely built bind proximal a membrane surface manner mostly unaffected large-scale steric hindrance. Biochemical studies proteoliposomes confirm importance lipid hydrophobic context binding 4E10, another recognizes gp41. Based on structural biochemical results, immunization strategies eliciting 2F5- 4E10-like proposed.