A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1

Kun-Wei Chan, Christina C. Luo, Hong Lu, Xueling Wu and Xiang-Peng Kong ()
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Kun-Wei Chan: NYU Grossman School of Medicine
Christina C. Luo: NYU Grossman School of Medicine
Hong Lu: Columbia University Vagelos College of Physicians and Surgeons
Xueling Wu: Columbia University Vagelos College of Physicians and Surgeons
Xiang-Peng Kong: NYU Grossman School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Identification of vulnerable sites defined by broadly neutralizing antibodies (bNAbs) on HIV-1 envelope (Env) is crucial for vaccine design, and we present here a vulnerable site defined by bNAb M4008_N1, which neutralizes about 40% of a tier-2 virus panel. A 3.2 Å resolution cryo-EM structure of M4008_N1 in complex with BG505 DS-SOSIP reveals a large, shallow protein epitope surface centered at the V3 crown of gp120 and surrounded by key glycans. M4008_N1 interacts with gp120 primarily through its hammerhead CDR H3 to form a β-sheet interaction with the V3 crown hairpin. This makes M4008_N1 compatible with the closed conformation of the prefusion Env trimer, and thus distinct from other known V3 crown mAbs. This mode of bNAb approaching the immunogenic V3 crown in the native Env trimer suggests a strategy for immunogen design targeting this site of vulnerability.

Date: 2021
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DOI: 10.1038/s41467-021-26846-z

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