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Production of Pseudotyped Particles to Study Highly Pathogenic Coronaviruses in a Biosafety Level 2 Setting
Published on: March 1, 2019
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Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly
Mandira Dutta1, Kimberly A Dolan2, Souad Amiar3
1Department of Chemistry, The University of Chicago, Chicago, IL 60637.
Biorxiv : the Preprint Server for Biology
|November 22, 2024
Summary
Coronaviruses
Area of Science:
- Virology
- Structural Biology
- Biochemistry
Background:
- The SARS-CoV-2 M protein is crucial for infectious virus particle formation.
- M protein exists in two conformations (Mshort and Mlong), with transitions potentially regulating viral assembly.
Purpose of the Study:
- To identify factors regulating M protein conformation and the roles of each state.
- To elucidate the interaction between M protein and sphingolipids.
Main Methods:
- Molecular dynamics simulations to study M protein conformational changes.
- Cryo-electron microscopy (Cryo-EM) to determine M protein structure.
- Biochemical assays to assess M protein interactions and function.
Main Results:
- Discovered a direct interaction between M protein and Golgi-enriched anionic lipids, specifically ceramide-1-phosphate (C1P).
- C1P binding stabilizes the Mshort conformation and promotes a transition from Mlong to Mshort.
- Cryo-EM revealed C1P binds to a conserved site on Mshort.
- Disruption of the Mshort-C1P interaction impaired viral assembly, reduced interactions with Spike and E proteins, and compromised virus-like particle entry.
Conclusions:
- Endogenous signaling lipids, like C1P, directly regulate M protein structure and dynamics.
- Mshort conformation is stabilized by C1P in the early endomembrane system, facilitating the organization of structural proteins for viral budding.
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