Structural studies of human HIV-1 V3 antibodies

Issue title: Humoral immune response against HIV-1

Guest editors: M.K. Gorny

Article type: Research Article

Authors: Stanfield, Robyn L.^{a; *} | Wilson, Ian A.^{a; b}

Affiliations: [a] Department of Molecular Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA | [b] The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA | New York University School of Medicine, c/o Veterans Affairs Medical Center, 423 East, 23rd Street, Room 18124N New York, NY 10010, USA

Correspondence: [*] Corresponding author. Tel.: +1 858 784 2234; Fax: +1 858 784 2980; E-mail: robyn@scripps.edu

Abstract: X-ray crystallographic structures of two human, anti-V3 HIV-1 neutralizing antibodies, 447-52D and 2219, show how the two antibodies use different strategies for their cross-reactivity with different V3 sequences. 447-52D recognizes V3 primarily through main-chain hydrogen bonds to the N-terminal side of V3, with the GPGR tip region buried in the antigen-combining site. The side chains on the N-terminal side of V3 are exposed to solvent, allowing for sequence changes in this region, thus explaining how 447-52D can neutralize a wide array of viral isolates. Antibody 2219 contacts a more extensive V3 surface, with more side-chain involvement. However, residues at the GPGR tip are exposed to solvent, with no constraints on residue size, so that binding to unusual tip sequences with larger side chains such as RPRQ is possible.

Keywords: HIV-1, neutralizing antibody, V3 loop, x-ray crystallography

DOI: 10.3233/HAB-2005-143-404

Journal: Human Antibodies, vol. 14, no. 3-4, pp. 73-80, 2005