Mostrar el registro sencillo del ítem
An allosteric switch between the activation loop and a c-terminal palindromic phosphomotif controls c-Src function.
dc.contributor.author | Cuesta-Hernández, Hipólito Nicolás | |
dc.contributor.author | Contreras, Julia | |
dc.contributor.author | Soriano Maldonado, Pablo | |
dc.contributor.author | Sánchez Wandelmer, Jana | |
dc.contributor.author | Yeung, Wayland | |
dc.contributor.author | Martín-Hurtado, Ana | |
dc.contributor.author | Muñoz, Inés G. | |
dc.contributor.author | Kannan, Natarajan | |
dc.contributor.author | Llimargas, Marta | |
dc.contributor.author | Muñoz, Javier | |
dc.contributor.author | Plaza-Menacho, Iván | |
dc.date.accessioned | 2023-12-15T13:05:42Z | |
dc.date.available | 2023-12-15T13:05:42Z | |
dc.date.issued | 2023 | |
dc.identifier.issn | 2041-1723 | spa |
dc.identifier.uri | https://hdl.handle.net/10641/3593 | |
dc.description.abstract | Autophosphorylation controls the transition between discrete functional and conformational states in protein kinases, yet the structural and molecular determinants underlying this fundamental process remain unclear. Here we show that c-terminal Tyr 530 is a de facto c-Src autophosphorylation site with slow time-resolution kinetics and a strong intermolecular component. On the contrary, activation-loop Tyr 419 undergoes faster kinetics and a cis-to-trans phosphorylation switch that controls c-terminal Tyr 530 autophosphorylation, enzyme specificity, and strikingly, c-Src non-catalytic function as a substrate. In line with this, we visualize by X-ray crystallography a snapshot of Tyr 530 intermolecular autophosphorylation. In an asymmetric arrangement of both catalytic domains, a c-terminal palindromic phospho-motif flanking Tyr 530 on the substrate molecule engages the G-loop of the active kinase adopting a position ready for entry into the catalytic cleft. Perturbation of the phosphomotif accounts for c-Src dysfunction as indicated by viral and colorectal cancer (CRC)-associated c-terminal deleted variants.Weshow that c-terminal residues 531 to 536 are required for c-Src Tyr 530 autophosphorylation, and such a detrimental effect is caused by the substrate molecule inhibiting allosterically the active kinase. Our work reveals a crosstalk between the activation and c-terminal segments that control the allosteric interplay between substrateand enzyme-acting kinases during autophosphorylation. | spa |
dc.language.iso | eng | spa |
dc.publisher | Nature Communications | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | An allosteric switch between the activation loop and a c-terminal palindromic phosphomotif controls c-Src function. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 5137 KB | spa |
dc.identifier.doi | 10.1038/s41467-023-41890-7 | spa |
dc.relation.publisherversion | https://www.nature.com/articles/s41467-023-41890-7 | spa |
Ficheros en el ítem
Este ítem aparece en la(s) siguiente(s) colección(ones)
-
CIENCIAS EXPERIMENTALES [323]