| http://purl.uniprot.org/citations/33852892 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33852892 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/33852892 | http://www.w3.org/2000/01/rdf-schema#comment | "The activation of cap-dependent translation in eukaryotes requires multisite, hierarchical phosphorylation of 4E-BP by the 1 MDa kinase mammalian target of rapamycin complex 1 (mTORC1). To resolve the mechanism of this hierarchical phosphorylation at the atomic level, we monitored by NMR spectroscopy the interaction of intrinsically disordered 4E binding protein isoform 1 (4E-BP1) with the mTORC1 subunit regulatory-associated protein of mTOR (Raptor). The N-terminal RAIP motif and the C-terminal TOR signaling (TOS) motif of 4E-BP1 bind separate sites in Raptor, resulting in avidity-based tethering of 4E-BP1. This tethering orients the flexible central region of 4E-BP1 toward the mTORC1 kinase site for phosphorylation. The structural constraints imposed by the two tethering interactions, combined with phosphorylation-induced conformational switching of 4E-BP1, explain the hierarchy of 4E-BP1 phosphorylation by mTORC1. Furthermore, we demonstrate that mTORC1 recognizes both free and eIF4E-bound 4E-BP1, allowing rapid phosphorylation of the entire 4E-BP1 pool and efficient activation of translation. Finally, our findings provide a mechanistic explanation for the differential rapamycin sensitivity of the 4E-BP1 phosphorylation sites."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.molcel.2021.03.031"xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.org/dc/terms/identifier | "doi:10.1016/j.molcel.2021.03.031"xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Maier T."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Maier T."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Jakob R.P."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Jakob R.P."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Hall M.N."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Hall M.N."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Hiller S."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Hiller S."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Imseng S."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Imseng S."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Bohm R."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/author | "Bohm R."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/date | "2021"xsd:gYear |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/name | "Mol. Cell"xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/name | "Mol Cell"xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/pages | "2403-2416.e5"xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/pages | "2403-2416.e5"xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/title | "The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1."xsd:string |
| http://purl.uniprot.org/citations/33852892 | http://purl.uniprot.org/core/title | "The dynamic mechanism of 4E-BP1 recognition and phosphorylation by mTORC1."xsd:string |