PXD035397

PXD035397 is an original dataset announced via ProteomeXchange.

Title	Irisin acts through its integrin receptor in a novel two-step process
Description	Exercise benefits the human body in many ways. Irisin is secreted by muscle, increased with exercise, and conveys many physiological benefits, including improved cognition and resistance to neurodegeneration. Irisin acts via αV integrins; however, a mechanistic understanding of how small polypeptides like irisin can signal through integrins is poorly understood. Using mass spectrometry and cryo-EM, we demonstrate that extracellular heat-shock protein 90α (eHsp90α) is secreted by muscle with exercise and acts as a required cofactor that “opens” the integrin αVβ5 structure to allows for high affinity irisin binding and signaling through an eHsp90α/αV/β5 complex. By including hydrogen/deuterium exchange data, we generate and experimentally validate a 2.98 Å RMSD irisin/αVβ5 complex docking model. Irisin binds very tightly to an alternative interface on αVβ5 distinct from that involved in its interaction with known ligands. These data together elucidate a non-canonical mechanism by which a small polypeptide hormone like irisin can function through integrins.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:48:31.265.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John R. Engen
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	2022-07-20 00:11:31	ID requested
1	2023-06-04 08:26:55	announced
⏵ 2	2023-11-14 08:48:32	announced	2023-11-14: Updated project metadata.

A M, Wales TE, Zhou H, Draga-Colet, ă SV, Gorgulla C, Blackmore KA, Mittenb, ü, hler MJ, Kim CR, Bogoslavski D, Zhang Q, Wang ZF, Jedrychowski MP, Seo HS, Song K, Xu AZ, Sebastian L, Gygi SP, Arthanari H, Dhe-Paganon S, Griffin PR, Engen JR, Spiegelman BM, . Mol Cell, 83(11):1903-1920.e12(2023) [pubmed]

submitter keyword: Irisin

Integrin

HDX-MS

hydrogen/deuterium exchange mass spectrometry

polypeptide hormone

αVβ5

John R. Engen
contact affiliation	Department of Chemistry and Chemical biology, Northeastern University
contact email	j.engen@northeastern.edu
lab head
John R. Engen
contact affiliation	Northeastern University
contact email	j.engen@northeastern.edu
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/2023/06/PXD035397

PRIDE project URI

• PRIDE
  1. PXD035397
     1. Label: PRIDE project
     2. Name: Irisin acts through its integrin receptor in a novel two-step process