8BWG
HRas (1-166) Y64 phosphorylation
Summary for 8BWG
| Entry DOI | 10.2210/pdb8bwg/pdb |
| Descriptor | GTPase HRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total) |
| Functional Keywords | small g protein, ras, post-translational modification, gtp binding protein, signalling, hydrolase |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 19438.76 |
| Authors | Baumann, P.,Jin, Y. (deposition date: 2022-12-06, release date: 2023-09-27, Last modification date: 2024-04-10) |
| Primary citation | Baumann, P.,Jin, Y. Far-reaching effects of tyrosine64 phosphorylation on Ras revealed with BeF 3 - complexes. Commun Chem, 7:19-19, 2024 Cited by PubMed Abstract: Tyrosine phosphorylation on Ras by Src kinase is known to uncouple Ras from upstream regulation and downstream communication. However, the mechanisms by which phosphorylation modulates these interactions have not been detailed. Here, the major mono-phosphorylation level on tyrosine64 is quantified by P NMR and mutagenesis. Crystal structures of unphosphorylated and tyrosine64-phosphorylated Ras in complex with a BeF ground state analogue reveal "closed" Ras conformations very different from those of the "open" conformations previously observed for non-hydrolysable GTP analogue structures of Ras. They deliver new mechanistic and conformational insights into intrinsic GTP hydrolysis. Phosphorylation of tyrosine64 delivers conformational changes distant from the active site, showing why phosphorylated Ras has reduced affinity to its downstream effector Raf. F NMR provides evidence for changes in the intrinsic GTPase and nucleotide exchange rate and identifies the concurrent presence of a major "closed" conformation alongside a minor yet functionally important "open" conformation at the ground state of Ras. This study expands the application of metal fluoride complexes in revealing major and minor conformational changes of dynamic and modified Ras proteins. PubMed: 38297137DOI: 10.1038/s42004-024-01105-6 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.32 Å) |
Structure validation
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