National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
AI158186
米国
引用
ジャーナル: Cell Host Microbe / 年: 2023 タイトル: Broad receptor tropism and immunogenicity of a clade 3 sarbecovirus. 著者: Jimin Lee / Samantha K Zepeda / Young-Jun Park / Ashley L Taylor / Joel Quispe / Cameron Stewart / Elizabeth M Leaf / Catherine Treichel / Davide Corti / Neil P King / Tyler N Starr / David Veesler / 要旨: 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. ...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.
履歴
登録
2023年9月5日
登録サイト: RCSB / 処理サイト: RCSB
改定 1.0
2023年12月6日
Provider: repository / タイプ: Initial release
改定 2.0
2023年12月27日
Group: Advisory / Atomic model ...Advisory / Atomic model / Author supporting evidence / Data collection / Database references / Derived calculations / Structure summary カテゴリ: atom_site / citation ...atom_site / citation / database_PDB_caveat / em_software / pdbx_entity_branch_descriptor / pdbx_entity_instance_feature / pdbx_entry_details / pdbx_struct_assembly / pdbx_struct_assembly_prop / pdbx_validate_polymer_linkage / struct_conf Item: _atom_site.Cartn_x / _atom_site.Cartn_y ..._atom_site.Cartn_x / _atom_site.Cartn_y / _atom_site.Cartn_z / _citation.journal_volume / _citation.page_first / _citation.page_last / _pdbx_entity_branch_descriptor.descriptor / _pdbx_entry_details.has_ligand_of_interest / _pdbx_struct_assembly.details / _pdbx_struct_assembly.method_details 解説: Polymer backbone linkage 詳細: This entry has not been released. It is a pre-release update Provider: author / タイプ: Coordinate replacement