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-Structure paper
タイトル | Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site. |
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ジャーナル・号・ページ | Structure, Vol. 30, Issue 6, Page 862-875.e4, Year 2022 |
掲載日 | 2022年6月2日 |
著者 | Tongqing Zhou / Lei Chen / Jason Gorman / Shuishu Wang / Young D Kwon / Bob C Lin / Mark K Louder / Reda Rawi / Erik-Stephane D Stancofski / Yongping Yang / Baoshan Zhang / Anna Forsman Quigley / Laura E McCoy / Lucy Rutten / Theo Verrips / Robin A Weiss / / Nicole A Doria-Rose / Lawrence Shapiro / Peter D Kwong / |
PubMed 要旨 | Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies ...Nanobodies can achieve remarkable neutralization of genetically diverse pathogens, including HIV-1. To gain insight into their recognition, we determined crystal structures of four llama nanobodies (J3, A12, C8, and D7), all of which targeted the CD4-binding site, in complex with the HIV-1 envelope (Env) gp120 core, and determined a cryoelectron microscopy (cryo-EM) structure of J3 with the Env trimer. Crystal and cryo-EM structures of J3 complexes revealed this nanobody to mimic binding to the prefusion-closed trimer for the primary site of CD4 recognition as well as a secondary quaternary site. In contrast, crystal structures of A12, C8, and D7 with gp120 revealed epitopes that included portions of the gp120 inner domain, inaccessible on the prefusion-closed trimer. Overall, these structures explain the broad and potent neutralization of J3 and limited neutralization of A12, C8, and D7, which utilized binding modes incompatible with the neutralization-targeted prefusion-closed conformation of Env. |
リンク | Structure / PubMed:35413243 / PubMed Central |
手法 | EM (単粒子) / X線回折 |
解像度 | 1.76 - 3.61 Å |
構造データ | EMDB-23480, PDB-7lpn: PDB-7r73: PDB-7r74: PDB-7ri1: PDB-7ri2: |
化合物 | ChemComp-NAG: ChemComp-HOH: ChemComp-SO4: |
由来 |
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キーワード | VIRAL PROTEIN / CD4 / HIV-1 / SOSIP / Vaccine / IMMUNE SYSTEM / llama / antibody / VHH / gp120 |