8U29

Prefusion structure of the PRD-0038 spike glycoprotein ectodomain trimer

Summary for 8U29

• Entry DOI: 10.2210/pdb8u29/pdb
• EMDB information: 41842
• Descriptor: PRD-0038 Spike glycoprotein, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 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, ... (5 entities in total)
• Functional Keywords: sarbecoviruses, spike glycoprotein, fusion protein, neutralizing antibodies, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• Biological source: Sarbecovirus sp.
• Total number of polymer chains: 3
• Total formula weight: 447001.88

Authors

Lee, J.,Park, Y.J.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2023-09-05, release date: 2023-12-06, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.8 Å)