PXD039760-2

PXD039760 is an original dataset announced via ProteomeXchange.

Title	Structural 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
Description	The 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.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:21.477.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Valeria Calvaresi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Synapt MS

Revision	Datetime	Status	ChangeLog Entry
0	2023-02-01 04:28:26	ID requested
1	2023-03-14 18:54:44	announced
⏵ 2	2023-11-14 09:00:22	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: SARS-CoV-2,Spike glycoprotein, HDX-MS

Argyris Politis
contact affiliation	Department 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 email	argyris.politis@manchester.ac.uk
lab head
Valeria Calvaresi
contact affiliation	King's College London
contact email	valeria.calvaresi@kcl.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/03/PXD039760

PRIDE project URI

• PRIDE
  1. PXD039760
     1. Label: PRIDE project
     2. Name: Structural 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