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Title | Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site. |
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Journal, issue, pages | Structure, Vol. 30, Issue 6, Page 862-875.e4, Year 2022 |
Publish date | Jun 2, 2022 |
Authors | 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 Abstract | 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. |
External links | Structure / PubMed:35413243 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 1.76 - 3.61 Å |
Structure data | EMDB-23480, PDB-7lpn: PDB-7r73: PDB-7r74: PDB-7ri1: PDB-7ri2: |
Chemicals | ChemComp-NAG: ChemComp-HOH: ChemComp-SO4: |
Source |
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Keywords | VIRAL PROTEIN / CD4 / HIV-1 / SOSIP / Vaccine / IMMUNE SYSTEM / llama / antibody / VHH / gp120 |