PXD035397 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
Publication List
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] |
Keyword List
submitter keyword: Irisin |
Integrin |
HDX-MS |
hydrogen/deuterium exchange mass spectrometry |
polypeptide hormone |
αVβ5 |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD035397
- Label: PRIDE project
- Name: Irisin acts through its integrin receptor in a novel two-step process