PXD015389

PXD015389 is an original dataset announced via ProteomeXchange.

Title	Sialic acid-mediated mechanical activation of β2 adrenergic receptors by bacterial pili
Description	Meningococcus utilizes β-arrestin selective activation of endothelial cell β2 adrenergic receptor (β2AR) to cause meningitis in humans. Molecular mechanisms of receptor activation by the pathogen and of its species selectivity remained elusive. We report that β2AR activation requires two asparagine-branched glycan chains with terminally exposed N-acetyl neuraminic acid (sialic acid, Neu5Ac) residues located at a specific distance in its N34 terminus, while being independent of surrounding amino-acid residues. Meningococcus triggers receptor signaling by exerting direct and hemodynamic-promoted traction forces on β2AR glycans. Similar activation is recapitulated with beads coated with Neu5Ac-binding lectins, submitted to mechanical stimulation. This previously unknown glycan-dependent mode of allosteric mechanical activation of a G protein-coupled receptor contributes to meningococcal species selectivity, since Neu5Ac is only abundant in humans due to the loss of CMAH, the enzyme converting Neu5Ac into N-glycolyl-neuraminic acid in other mammals. It represents an additional mechanism of evolutionary adaptation of a pathogen to its host.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:57:42.514.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-09-10 01:49:03	ID requested
1	2019-11-11 18:23:07	announced
⏵ 2	2024-10-22 04:57:50	announced	2024-10-22: Updated project metadata.

Virion Z, Doly S, Saha K, Lambert M, Guillonneau F, Bied C, Duke RM, Rudd PM, Robbe-Masselot C, Nassif X, Coureuil M, Marullo S, adrenergic receptors by bacterial pili. Nat Commun, 10(1):4752(2019) [pubmed]

10.1038/s41467-019-12685-6;

submitter keyword: Proline effect,human β-adrenergic receptor, pilin, Q-exactive, Blood-Brain Barrier, internal fragments, N-Glycan

Stephano Marullo M.D. Ph.D.
contact affiliation	Université de Paris, Institut Cochin, Inserm, U1016, CNRS UMR8104, Paris, France
contact email	stefano.marullo@inserm.fr
lab head
François GUILLONNEAU
contact affiliation	ICO Angers
contact email	francois.guillonneau@parisdescartes.fr
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/2019/11/PXD015389

PRIDE project URI

• PRIDE
  1. PXD015389
     1. Label: PRIDE project
     2. Name: Sialic acid-mediated mechanical activation of β2 adrenergic receptors by bacterial pili