8BWG

HRas (1-166) Y64 phosphorylation

8BWG の概要

• エントリーDOI: 10.2210/pdb8bwg/pdb
• 分子名称: GTPase HRas, GUANOSINE-5'-DIPHOSPHATE, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: small g protein, ras, post-translational modification, gtp binding protein, signalling, hydrolase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19438.76

構造登録者

Baumann, P.,Jin, Y. (登録日: 2022-12-06, 公開日: 2023-09-27, 最終更新日: 2024-04-10)

主引用文献

Baumann, P.,Jin, Y.
Far-reaching effects of tyrosine64 phosphorylation on Ras revealed with BeF 3 - complexes.
Commun Chem, 7:19-19, 2024

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: 38297137
DOI: 10.1038/s42004-024-01105-6

実験手法

X-RAY DIFFRACTION (1.32 Å)