6F3F
Autoinhibited Src kinase bound to ADP
Summary for 6F3F
| Entry DOI | 10.2210/pdb6f3f/pdb |
| Descriptor | Tyrosine-protein kinase, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total) |
| Functional Keywords | kinase, adp, autoinhibited, signaling protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 1 |
| Total formula weight | 52489.42 |
| Authors | von Raussendorf, F.,Leonard, T.A. (deposition date: 2017-11-28, release date: 2017-12-27, Last modification date: 2024-10-23) |
| Primary citation | von Raussendorf, F.,de Ruiter, A.,Leonard, T.A. A switch in nucleotide affinity governs activation of the Src and Tec family kinases. Sci Rep, 7:17405-17405, 2017 Cited by PubMed Abstract: The Tec kinases, closely related to Src family kinases, are essential for lymphocyte function in the adaptive immune system. Whilst the Src and Abl kinases are regulated by tail phosphorylation and N-terminal myristoylation respectively, the Tec kinases are notable for the absence of either regulatory element. We have found that the inactive conformations of the Tec kinase Itk and Src preferentially bind ADP over ATP, stabilising both proteins. We demonstrate that Itk adopts the same conformation as Src and that the autoinhibited conformation of Src is independent of its C-terminal tail. Allosteric activation of both Itk and Src depends critically on the disruption of a conserved hydrophobic stack that accompanies regulatory domain displacement. We show that a conformational switch permits the exchange of ADP for ATP, leading to efficient autophosphorylation and full activation. In summary, we propose a universal mechanism for the activation and autoinhibition of the Src and Tec kinases. PubMed: 29234112DOI: 10.1038/s41598-017-17703-5 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.41795770496 Å) |
Structure validation
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