Structural characterization of a highly-potent V3-glycan broadly neutralizing antibody bound to natively-glycosylated HIV-1 envelope [electronic resource]

• Ngôn ngữ: eng
• Ký hiệu phân loại: 577.2 Specific factors affecting ecology
• Thông tin xuất bản: Oak Ridge, Tenn. : Distributed by the Office of Scientific and Technical Information, U.S. Dept. of Energy, 2018
• Mô tả vật lý: Size: Article No. 1251 : , digital, PDF file.
• Bộ sưu tập: Metadata
• ID: 260247
• Chủ đề: 1. 59 basic biological sciences; 2. 60 applied life sciences; 3. Glycoproteins; 4. Hiv infections; 5. Science & technology - other topics; 6. X-ray crystallography

Tóm tắt

 Broadly neutralizing antibodies (bNAbs) isolated from HIV-1-infected individuals inform HIV-1 vaccine design efforts. Developing bNAbs with increased efficacy requires understanding how antibodies interact with the native oligomannose and complex-type N-glycan shield that hides most protein epitopes on HIV-1 envelope (Env). Here we present crystal structures, including a 3.8-� X-ray free electron laser dataset, of natively glycosylated Env trimers complexed with BG18, the most potent V3/N332<
 sub>
 gp120<
 /sub>
  glycan-targeting bNAb reported to date. Our structures show conserved contacts mediated by common D gene-encoded residues with the N332<
 sub>
 gp120<
 /sub>
  glycan and the gp120 GDIR peptide motif, but a distinct Env-binding orientation relative to PGT121/10-1074 bNAbs. BG18?s binding orientation provides additional contacts with N392<
 sub>
 gp120<
 /sub>
  and N386<
 sub>
 gp120<
 /sub>
  glycans near the V3-loop base and engages protein components of the V1-loop. The BG18-natively-glycosylated Env structures facilitate understanding of bNAb?glycan interactions critical for using V3/N332<
 sub>
 gp120<
 /sub>
  bNAbs therapeutically and targeting their epitope for immunogen design.