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PXD039760

PXD039760 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleStructural dynamics in the evolution of SARS-CoV-2 spike glycoprotein: HDX-MS analysis of the spike of the original Wuhan isolate, G614 spike mutant, and the isolated ancestral RBD - in apo state and in complex with the ACE2 receptor
DescriptionThe spike glycoprotein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mediates binding to the ACE2 receptor and subsequent membrane fusion. It exists in a range of conformations, including a closed state unable to bind the ACE2 receptor, and an open state that does so but displays more exposed antigenic surface. Spikes of variants of concern (VOCs) acquired amino acid changes linked to different opening probabilities, increased SARS-CoV-2 virulence and immune evasion. Here, using hydrogen-deuterium exchange mass spectrometry (HDX-MS), we analyzed the spike of the original Wuhan isolate, G614 mutant, spike of alpha, beta, delta and omicron VOCs and the isolated ancestral receptor binding domain (RBD) - in apo state and in complex with the ACE2 receptor. We identified changes in spike dynamics that we associated with the transition from closed to open conformation, to ACE2 binding, and to specific mutations in VOCs. We show that the RBD-associated subdomain plays a role in spike opening, whereas the NTD acts as a hotspot of conformational divergence of VOC spikes driving immune evasion. Alpha, beta and delta spikes assume predominantly open conformations and a strong ACE2 binding increases the dynamics of their core helices, priming spikes for fusion. Conversely, substitutions in omicron spike lead to predominantly binding-incompetent closed conformations, presumably enabling it to escape antibodies. At the same time, its core helices show characteristics of being pre-primed for fusion even in the absence of ACE2. These data inform on SARS-CoV-2 evolution and omicron variant emergence.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_09:00:21.477.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterValeria Calvaresi
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentSynapt MS
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-02-01 04:28:26ID requested
12023-03-14 18:54:44announced
22023-11-14 09:00:22announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: SARS-CoV-2,Spike glycoprotein, HDX-MS
Contact List
Argyris Politis
contact affiliationDepartment of Chemistry, King’s College London, SE1 1DB, London, UK Faculty of Biology, Medicine and Health, School of Biological Sciences, The University of Manchester, M13 9PT, Manchester, UK Manchester Institute of Biotechnology, The University of Manchester, M1 7DN, Manchester, UK
contact emailargyris.politis@manchester.ac.uk
lab head
Valeria Calvaresi
contact affiliationKing's College London
contact emailvaleria.calvaresi@kcl.ac.uk
dataset submitter
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Dataset FTP location
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