9CX9
Structure of SH3 domain of Src in complex with beta-arrestin 1
Summary for 9CX9
| Entry DOI | 10.2210/pdb9cx9/pdb |
| Related | 9BT8 9CX3 |
| EMDB information | 45982 |
| Descriptor | Antibody fragment Fab30, heavy chain, Antibody fragment Fab30, light chain, Vasopressin V2 receptor, ... (5 entities in total) |
| Functional Keywords | gpcr signaling, arrestin, src, sh3, signaling protein |
| Biological source | Mus musculus (house mouse) More |
| Total number of polymer chains | 5 |
| Total formula weight | 106304.08 |
| Authors | Pakharukova, N.,Bansia, H.,Lefkowitz, R.J.,des Georges, A. (deposition date: 2024-07-31, release date: 2024-11-13, Last modification date: 2026-03-04) |
| Primary citation | 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, 2026 Cited by 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: 41720803DOI: 10.1038/s41467-026-69884-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.34 Å) |
Structure validation
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