PXD079401-1

PXD079401 is an original dataset announced via ProteomeXchange.

Title	Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly
Description	M is the most abundant structural membrane protein in coronaviruses and is essential for the formation of infectious virus particles. SARS-CoV-2 M adopts two conformations, Mshort and Mlong, and regulated transition between states is hypothesized to coordinate viral assembly and budding. However, the factors that regulate M conformation and roles for each state are unknown. Here, we discover a direct M-sphingolipid interaction that controls M conformational dynamics, interaction with other structural proteins, and virus assembly. We show M binds Golgi-enriched anionic lipids including ceramide-1-phosphate (C1P). Molecular dynamics simulations show C1P interaction promotes a long to short transition and energetically stabilizes Mshort. Cryo-EM structures show C1P specifically binds Mshort at a conserved site bridging transmembrane and cytoplasmic regions. Hydrogen-deuterium exchange mass spectrometry confirms that C1P binds primarily to a condensed Mshort conformation and shows a switching from Mshort to Mlong in virus-like particles. Disrupting Mshort-C1P interaction alters M subcellular localization, reduces colocalization with Spike and E, and reduces virus-like particle formation and cell entry. Together, these results show endogenous signaling lipids regulate M structure and support a model in which Mshort is stabilized in the early endomembrane system to organize other structural proteins prior to viral budding.
HostingRepository	PRIDE
AnnounceDate	2026-07-09
AnnouncementXML	Submission_2026-07-09_06:29:13.744.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sean Braet
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	No PTMs are included in the dataset
Instrument	SYNAPT G2-Si; SELECT SERIES Cyclic IMS

Revision	Datetime	Status	ChangeLog Entry
0	2026-06-08 08:08:54	ID requested
⏵ 1	2026-07-09 06:29:14	announced

Dataset with its publication pending

submitter keyword: HDXMS, SARS-CoV-2, lipid interaction

Dr. Ganesh S. Anand
contact affiliation	Pennsylvania State University, Department of Chemistry
contact email	gsa5089@psu.edu
lab head
Sean Braet
contact affiliation	Penn State
contact email	smb6745@psu.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD079401
     1. Label: PRIDE project
     2. Name: Direct lipid interactions control SARS-CoV-2 M protein conformational dynamics and virus assembly