Structural basis of clade-specific HIV-1 neutralization by humanized anti-V3 monoclonal antibody KD-247
作者： Karen A. Kirby , Yee Tsuey Ong , Atsuko Hachiya , Thomas G. Laughlin , Leslie A. Chiang
DOI: 10.1096/FJ.14-252262
关键词:
摘要: Humanized monoclonal antibody KD-247 targets the Gly(312)-Pro(313)-Gly(314)-Arg(315) arch of third hypervariable (V3) loop HIV-1 surface glycoprotein. It potently neutralizes many clade B isolates, but not other clades. To understand molecular basis this specificity, we solved a high-resolution (1.55 A) crystal structure antigen binding fragment and examined potential interactions with various V3 targets. Unlike most antibodies, appears to interact its target primarily through light chain residues. Several these involve Arg(315) loop. evaluate role residues in recognition loop, generated 20 variants single-chain variable fragments mutations antigen-binding site. Purified proteins were assessed for using AlphaScreen technology neutralization. Our data revealed that clade-specificity defining residue is based on network Tyr(L32), Tyr(L92), Asn(L27d) directly Arg(315), thus elucidating target.
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