9CX3

Structure of SH3 domain of Src in complex with beta-arrestin 1

9CX3 の概要

• エントリーDOI: 10.2210/pdb9cx3/pdb
• 関連するPDBエントリー: 9B78
• EMDBエントリー: 45977
• 分子名称: Nanobody 32, Proto-oncogene tyrosine-protein kinase Src, Antibody fragment Fab30, heavy chain, ... (6 entities in total)
• 機能のキーワード: gpcr signaling, arrestin, src, sh3, signaling protein-immune system complex, signaling protein
• 由来する生物種: Lama glama; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 120001.22

構造登録者

Pakharukova, N.,Bansia, H.,des Georges, A.,Lefkowitz, R.J. (登録日: 2024-07-30, 公開日: 2024-11-13, 最終更新日: 2026-04-08)

主引用文献

Pakharukova, N.,Thomas, B.N.,Bansia, H.,Li, L.,Bassford, D.K.,Abzalimov, R.R.,Kim, J.,Kahsai, A.W.,Pani, B.,Xiao, K.,Ochakovski, R.,Liu, S.,Zhang, X.,Ahn, S.,des Georges, A.,Lefkowitz, R.J.
Mechanism of beta-arrestin 1 mediated Src activation via Src SH3 domain revealed by cryo-electron microscopy.
Nat Commun, 17:-, 2026

PubMed Abstract: 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 delineate structural mechanisms underlying βarr-mediated signal transduction. Using cryo-electron microscopy, we elucidate how βarr1 recruits and activates the non-receptor tyrosine kinase Src, a well-established 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.

PubMed: 41720803
DOI: 10.1038/s41467-026-69884-1

実験手法

ELECTRON MICROSCOPY (3.47 Å)