8XZ5

SARS-CoV-2 S and moesin complex structure

Summary for 8XZ5

• Entry DOI: 10.2210/pdb8xz5/pdb
• Descriptor: Moesin, Spike protein S2' (3 entities in total)
• Functional Keywords: sars-cov-2, s, ezrin-radixin-moesin, cytoskeleton, assembly, viral protein/protein binding, viral proein-protein binding complex, viral proein/protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 36461.06

Authors

Wang, J.M.,Ma, W.F. (deposition date: 2024-01-20, release date: 2025-10-08, Last modification date: 2026-04-22)

Primary citation

Wang, J.,Tai, W.,Wang, Z.,Dai, W.,Yang, M.,Guo, J.,He, P.,Nan, Y.,Li, T.,Zhou, S.,Cui, D.,Li, Y.,Ma, C.,Zhang, Y.,Li, D.,Zhu, Z.,Chu, K.,Wang, D.,Yang, S.,Zhuang, X.,Tian, M.,Huang, M.,Zhang, X.,Cheng, G.,Ma, W.
SARS-CoV-2 S assembly into virions facilitated by host ERM proteins.
Proc.Natl.Acad.Sci.USA, 123:e2504517123-e2504517123, 2026

PubMed Abstract: The host cell cytoskeleton plays a critical role in the SARS-CoV-2 life cycle, though the underlying mechanisms remain poorly understood. This study investigates the interaction between the SARS-CoV-2 spike (S) protein and the cytoskeleton-associated ezrin-radixin-moesin (ERM) proteins through biochemical and structural characterization. A previously unidentified ERM-binding motif on the SARS-CoV-2 S protein is identified, revealing that S-ERM interactions are specifically conserved among highly pathogenic coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2. Functionally, these interactions facilitate S packaging into virions by directing it to assembly sites, utilizing ERM's affinity for negatively curved membranes, akin to its role in cell surface protrusions. Silencing ERM expression significantly reduces SARS-CoV-2 titer, highlighting its essential role in viral propagation. Additionally, leveraging the established role of COPI-mediated trafficking in S localization, a compound is developed to disrupt S-COPI binding, promoting S secretion to the cell surface and effectively reducing viral titers. Our findings revealed a critical host-pathogen interaction that drives S incorporation into virions and identified ERM proteins as key facilitators of coronavirus assembly. Furthermore, our study suggests an antiviral strategy by targeting the S-COPI trafficking pathway. These insights advanced our understanding of coronavirus-host interactions and provided a potential therapeutic approach against SARS-CoV-2 and other highly pathogenic coronaviruses.

PubMed: 41615754
DOI: 10.1073/pnas.2504517123

Experimental method

X-RAY DIFFRACTION (1.8 Å)