8U0T

PRD-0038 RBD bound to Rhinolophus alcyone ACE2 (local refinement)

8U0T の概要

• エントリーDOI: 10.2210/pdb8u0t/pdb
• EMDBエントリー: 41784 41786
• 分子名称: Angiotensin-converting enzyme, PRD-0038, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: sarbecoviruses, spike glycoprotein, fusion protein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, inhibitor, viral protein
• 由来する生物種: Rhinolophus alcyone (Halcyon horseshoe bat); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 119716.01

構造登録者

Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (登録日: 2023-08-29, 公開日: 2023-12-06, 最終更新日: 2024-10-23)

主引用文献

Lee, J.,Zepeda, S.K.,Park, Y.J.,Taylor, A.L.,Quispe, J.,Stewart, C.,Leaf, E.M.,Treichel, C.,Corti, D.,King, N.P.,Starr, T.N.,Veesler, D.
Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus.
Cell Host Microbe, 31:1961-1973.e11, 2023

PubMed Abstract: Although Rhinolophus bats harbor diverse clade 3 sarbecoviruses, the structural determinants of receptor tropism along with the antigenicity of their spike (S) glycoproteins remain uncharacterized. Here, we show that the African Rhinolophus bat clade 3 sarbecovirus PRD-0038 S has a broad angiotensin-converting enzyme 2 (ACE2) usage and that receptor-binding domain (RBD) mutations further expand receptor promiscuity and enable human ACE2 utilization. We determine a cryo-EM structure of the PRD-0038 RBD bound to Rhinolophus alcyone ACE2, explaining receptor tropism and highlighting differences with SARS-CoV-1 and SARS-CoV-2. Characterization of PRD-0038 S using cryo-EM and monoclonal antibody reactivity reveals its distinct antigenicity relative to SARS-CoV-2 and identifies PRD-0038 cross-neutralizing antibodies for pandemic preparedness. PRD-0038 S vaccination elicits greater titers of antibodies cross-reacting with vaccine-mismatched clade 2 and clade 1a sarbecoviruses compared with SARS-CoV-2 S due to broader antigenic targeting, motivating the inclusion of clade 3 antigens in next-generation vaccines for enhanced resilience to viral evolution.

PubMed: 37989312
DOI: 10.1016/j.chom.2023.10.018

実験手法

ELECTRON MICROSCOPY (3.2 Å)