8VKP

Cryo-EM structure of SARS-CoV-2 XBB.1.5 spike protein in complex with human ACE2 (focused refinement of RBD and ACE2)

Summary for 8VKP

• Entry DOI: 10.2210/pdb8vkp/pdb
• EMDB information: 43325
• Descriptor: Spike protein S1, Processed angiotensin-converting enzyme 2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: complex, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 2
• Total formula weight: 94922.36

Authors

Zhu, X.,Mannar, D.,Saville, J.,Poloni, C.,Bezeruk, A.,Tidey, K.,Ahmed, S.,Tuttle, K.,Vahdatihassani, F.,Cholak, S.,Cook, L.,Steiner, T.S.,Subramaniam, S. (deposition date: 2024-01-09, release date: 2024-02-14, Last modification date: 2025-02-26)

Primary citation

Mannar, D.,Saville, J.W.,Poloni, C.,Zhu, X.,Bezeruk, A.,Tidey, K.,Ahmed, S.,Tuttle, K.S.,Vahdatihassani, F.,Cholak, S.,Cook, L.,Steiner, T.S.,Subramaniam, S.
Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein.
Nat Commun, 15:1854-1854, 2024

PubMed Abstract: The XBB.1.5 variant of SARS-CoV-2 has rapidly achieved global dominance and exhibits a high growth advantage over previous variants. Preliminary reports suggest that the success of XBB.1.5 stems from mutations within its spike glycoprotein, causing immune evasion and enhanced receptor binding. We present receptor binding studies that demonstrate retention of binding contacts with the human ACE2 receptor and a striking decrease in binding to mouse ACE2 due to the revertant R493Q mutation. Despite extensive evasion of antibody binding, we highlight a region on the XBB.1.5 spike protein receptor binding domain (RBD) that is recognized by serum antibodies from a donor with hybrid immunity, collected prior to the emergence of the XBB.1.5 variant. T cell assays reveal high frequencies of XBB.1.5 spike-specific CD4 and CD8 T cells amongst donors with hybrid immunity, with the CD4 T cells skewed towards a Th1 cell phenotype and having attenuated effector cytokine secretion as compared to ancestral spike protein-specific cells. Thus, while the XBB.1.5 variant has retained efficient human receptor binding and gained antigenic alterations, it remains susceptible to recognition by T cells induced via vaccination and previous infection.

PubMed: 38424106
DOI: 10.1038/s41467-024-46104-2

Experimental method

ELECTRON MICROSCOPY (2.77 Å)