PXD028071

PXD028071 is an original dataset announced via ProteomeXchange.

Title	Deamidation drives molecular aging of the SARS-CoV-2 spike receptor-binding motif
Description	The spike is the main protein component of the SARS-CoV-2 virion surface. The spike receptor-binding motif mediates recognition of the hACE2 receptor, a critical infection step, and is the preferential target for spike-neutralizing antibodies. Post-translational modifications of the spike receptor-binding motif can modulate viral infectivity and immune response. We studied the spike protein searching for asparagine deamidation, a spontaneous event that leads to the appearance of aspartic and isoaspartic residues, affecting both the protein backbone and its charge. We used computational prediction and biochemical experiments to identify five deamidation hotspots in the SARS-CoV-2 spike. Asparagine residues 481 and 501 from the receptor-binding motif deamidate with a half-time of 16.5 and 123 days at 37 °C, respectively. Deamidation is significantly slowed down at 4 °C, pointing at a strong dependence of spike molecular aging on the environmental conditions. We demonstrate that topological constraints drive the conservation of deamidation hotspots among Sarbecoviruses spike proteins. Deamidation of the spike receptor-binding motif decreases the equilibrium constant for binding to the hACE2 receptor more than 3.5-fold, yet its high conservation pattern suggests some positive effect on viral fitness. We propose a model for deamidation of the full SARS-CoV-2 virion that illustrates how deamidation of the spike receptor-binding motif leads to the accumulation on the virion surface of a non-negligible chemically diverse spike population in a timescale of days. Our findings provide a mechanism for molecular aging of the spike, with significant consequences for understanding virus infectivity and vaccine development.
HostingRepository	PRIDE
AnnounceDate	2022-02-15
AnnouncementXML	Submission_2022-02-15_06:51:32.683.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jennifer Schwarz
SpeciesList	scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: 2697049;
ModificationList	deamidated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2021-08-23 06:43:45	ID requested
⏵ 1	2022-02-15 06:51:33	announced

Lorenzo R, Defelipe LA, Aliperti L, Niebling S, Cust, ó, dio TF, L, ö, w C, Schwarz JJ, Remans K, Craig PO, Otero LH, Klinke S, Garc, í, a-Alai M, S, á, nchez IE, Alonso LG, Deamidation drives molecular aging of the SARS-CoV-2 spike protein receptor-binding motif. J Biol Chem, 297(4):101175(2021) [pubmed]

ProteomeXchange project tag: Covid-19

submitter keyword: SARS-CoV-2, RBD, deamidation, molecular aging

Leonardo G.Alonso
contact affiliation	Instituto de Nanobiotecnologıa (NANOBIOTEC), UBA-CONICET-Universidad de Buenos Aires, Buenos Aires, Argentina
contact email	lalonso@docente.ffyb.uba.ar
lab head
Jennifer Schwarz
contact affiliation	European Molecular Biology Laboratory, Heidelberg, Meyerhofstraße 1, 69117 Heidelberg, Germany
contact email	jennifer.schwarz@embl.de
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/2022/02/PXD028071

PRIDE project URI

• PRIDE
  1. PXD028071
     1. Label: PRIDE project
     2. Name: Deamidation drives molecular aging of the SARS-CoV-2 spike receptor-binding motif