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Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.

Zhou T, Chen L, Gorman J, Wang S, Kwon YD, Lin BC, Louder MK, Rawi R, Stancofski ED, Yang Y, Zhang B, Quigley AF, McCoy LE, Rutten L, Verrips T, Weiss RA, Doria-Rose NA, Shapiro L, Kwong PD
Structure 30 862-875.e4 (2022)
Related entries: 7r73, 7r74, 7ri1, 7ri2

Cited: 3 times
EuropePMC logo PMID: 35413243

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 (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.

Articles - 7lpn mentioned but not cited (1)

  1. Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site. Zhou T, Chen L, Gorman J, Wang S, Kwon YD, Lin BC, Louder MK, Rawi R, Stancofski ED, Yang Y, Zhang B, Quigley AF, McCoy LE, Rutten L, Verrips T, Weiss RA, VRC Production Program, Doria-Rose NA, Shapiro L, Kwong PD. Structure 30 862-875.e4 (2022)


Articles citing this publication (2)

  1. Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency. Zhang B, Gorman J, Kwon YD, Pegu A, Chao CW, Liu T, Asokan M, Bender MF, Bylund T, Damron L, Gollapudi D, Lei P, Li Y, Liu C, Louder MK, McKee K, Olia AS, Rawi R, Schön A, Wang S, Yang ES, Yang Y, Carlton K, Doria-Rose NA, Shapiro L, Seaman MS, Mascola JR, Kwong PD. MAbs 15 2165390 (2023)
  2. Identification of two novel neutralizing nanobodies against swine hepatitis E virus. Chen Y, Wang X, Zhang M, Li J, Gao X, Nan Y, Zhao Q, Zhou EM, Liu B. Front Microbiol 13 1048180 (2022)


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