9EHM

Structure of HIV-1 BG505 SOSIP.664 Env trimer in complex with IOMAmin5 and 10-1074 Broadly Neutralizing Antibodies - Class II

9EHM の概要

• エントリーDOI: 10.2210/pdb9ehm/pdb
• EMDBエントリー: 48060
• 分子名称: HIV-1 BG505 SOSIP gp120,Envelope glycoprotein gp120, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (13 entities in total)
• 機能のキーワード: hiv-1, env, bnab, viral protein-immune system complex, viral protein/immune system
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 373969.97

構造登録者

Dam, K.A.,Yang, Z.,Bjorkman, P.J. (登録日: 2024-11-23, 公開日: 2025-05-21, 最終更新日: 2025-05-28)

主引用文献

Dam, K.A.,Gristick, H.B.,Li, Y.E.,Yang, Z.,Gnanapragasam, P.N.P.,West Jr., A.P.,Seaman, M.S.,Bjorkman, P.J.
Mapping essential somatic hypermutations in a CD4-binding site bNAb informs HIV-1 vaccine design.
Cell Rep, 44:115713-115713, 2025

PubMed Abstract: HIV-1 broadly neutralizing antibodies (bNAbs) targeting the CD4-binding site (CD4bs) contain rare features that pose challenges to elicit these bNAbs through vaccination. The IOMA class of CD4bs bNAbs includes fewer rare features and somatic hypermutations (SHMs) to achieve broad neutralization, thus presenting a potentially accessible pathway for vaccine-induced bNAb development. Here, we created a library of IOMA variants in which each SHM was individually reverted to the inferred germline counterpart to investigate the roles of SHMs in conferring IOMA's neutralization potency and breadth. Impacts on neutralization for each variant were evaluated, and this information was used to design minimally mutated IOMA-class variants (IOMAmin) that incorporated the fewest SHMs required for achieving IOMA's neutralization breadth. A cryoelectron microscopy (cryo-EM) structure of an IOMAmin variant bound to Env was used to further interpret characteristics of IOMA variants to elucidate how IOMA's structural features correlate with its neutralization mechanism, informing the design of IOMA-targeting immunogens.

PubMed: 40378041
DOI: 10.1016/j.celrep.2025.115713

実験手法

ELECTRON MICROSCOPY (4.2 Å)