PXD073058

PXD073058 is an original dataset announced via ProteomeXchange.

Title	Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy
Description	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 report the first structural insights into the fundamental mechanisms driving βarr-mediated signal transduction. Using cryo-electron microscopy, we elucidate how βarr1 recruits and activates the non-receptor tyrosine kinase Src, the first identified signaling partner of βarrs. βarr1 engages Src SH3 through two distinct sites, each employing a different recognition mechanism: a polyproline motif in the N-domain and a non-proline-based interaction in the central crest region. At both sites βarr1 interacts with the aromatic surface of SH3, disrupting the autoinhibited conformation of Src and directly triggering its allosteric activation. This structural evidence establishes βarr1 as an active regulatory protein rather than a passive scaffold and suggests a potentially general mechanism for βarr-mediated signaling across diverse effectors.
HostingRepository	PRIDE
AnnounceDate	2026-01-27
AnnouncementXML	Submission_2026-01-26_19:16:12.185.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kunhong Xiao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	No PTMs are included in the dataset
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2026-01-14 07:21:35	ID requested
⏵ 1	2026-01-26 19:16:13	announced

10.1101/2024.07.31.605623;

Pakharukova N, Thomas BN, Bansia H, Li L, Bassford DK, Abzalimov RR, Kim J, Kahsai AW, Pani B, Xiao K, Ochakovski R, Liu S, Zhang X, Ahn S, des Georges A, Lefkowitz RJ, Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy. bioRxiv, ():(2025) [pubmed]

submitter keyword: Src activation,beta-arrestin, CXMS, Src, LC-MS/MS

Kunhong Xiao
contact affiliation	Center for Proteomics & Artificial Intelligence, Allegheny Health Network Cancer Institute, Pittsburgh, PA 15202, USA
contact email	kevin.kh.xiao@gmail.com
lab head
Kunhong Xiao
contact affiliation	AHN
contact email	kevin.kh.xiao@gmail.com
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/2026/01/PXD073058

PRIDE project URI

• PRIDE
  1. PXD073058
     1. Label: PRIDE project
     2. Name: Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy