Beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.


Journal

bioRxiv : the preprint server for biology
ISSN: 2692-8205
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
06 Aug 2024
Historique:
medline: 12 8 2024
pubmed: 12 8 2024
entrez: 12 8 2024
Statut: epublish

Résumé

Beta-arrestins (βarrs) are key regulators and transducers of G-protein coupled receptor signaling; however, little is known of how βarrs communicate with their downstream effectors. Here, we use cryo-electron microscopy to elucidate how βarr1 recruits and activates non-receptor tyrosine kinase Src. βarr1 binds Src SH3 domain via two distinct sites: a polyproline site in the N-domain and a non-proline site in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3 which is critical for Src autoinhibition, suggesting that βarr1 activates Src by SH3 domain displacement. Binding of SH3 to the central crest region induces structural rearrangements in the β-strand V, finger, and middle loops of βarr1 and interferes with βarr1 coupling to the receptor core potentially impacting receptor desensitization and downstream signaling. Beta-arrestin 1 uses two distinct sites to bind the SH3 domain of Src and drive relief of Src autoinhibition.

Identifiants

pubmed: 39131402
doi: 10.1101/2024.07.31.605623
pmc: PMC11312540
pii:
doi:

Types de publication

Journal Article Preprint

Langues

eng

Auteurs

Classifications MeSH