5B30

H-Ras WT in complex with GppNHp (state 1) after structural transition by humidity control

5B30 の概要

• エントリーDOI: 10.2210/pdb5b30/pdb
• 関連するPDBエントリー: 5B2Z
• 分子名称: GTPase HRas, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, MAGNESIUM ION, ... (6 entities in total)
• 機能のキーワード: oncoprotein
• 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: 19936.29

構造登録者

Kumasaka, T.,Miyano, N.,Baba, S.,Matsumoto, S.,Kataoka, T.,Shima, F. (登録日: 2016-02-08, 公開日: 2016-06-01, 最終更新日: 2023-11-08)

主引用文献

Matsumoto, S.,Miyano, N.,Baba, S.,Liao, J.,Kawamura, T.,Tsuda, C.,Takeda, A.,Yamamoto, M.,Kumasaka, T.,Kataoka, T.,Shima, F.
Molecular Mechanism for Conformational Dynamics of Ras-GTP Elucidated from In-Situ Structural Transition in Crystal
Sci Rep, 6:25931-25931, 2016

PubMed Abstract: Ras•GTP adopts two interconverting conformational states, state 1 and state 2, corresponding to inactive and active forms, respectively. However, analysis of the mechanism for state transition was hampered by the lack of the structural information on wild-type Ras state 1 despite its fundamental nature conserved in the Ras superfamily. Here we solve two new crystal structures of wild-type H-Ras, corresponding to state 1 and state 2. The state 2 structure seems to represent an intermediate of state transition and, intriguingly, the state 1 crystal is successfully derived from this state 2 crystal by regulating the surrounding humidity. Structural comparison enables us to infer the molecular mechanism for state transition, during which a wide range of hydrogen-bonding networks across Switch I, Switch II and the α3-helix interdependently undergo gross rearrangements, where fluctuation of Tyr32, translocation of Gln61, loss of the functional water molecules and positional shift of GTP play major roles. The NMR-based hydrogen/deuterium exchange experiments also support this transition mechanism. Moreover, the unveiled structural features together with the results of the biochemical study provide a new insight into the physiological role of state 1 as a stable pool of Ras•GTP in the GDP/GTP cycle of Ras.

PubMed: 27180801
DOI: 10.1038/srep25931

実験手法

X-RAY DIFFRACTION (1.6 Å)