1ZVQ

Structure of the Q61G mutant of Ras in the GDP-bound form

1ZVQ の概要

• エントリーDOI: 10.2210/pdb1zvq/pdb
• 関連するPDBエントリー: 1LF5 1ZW6 4Q21
• 分子名称: Transforming protein p21/H-Ras-1, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: gtpase, gdp, oncoprotein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane. Isoform 2: Nucleus: P01112
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19295.93

構造登録者

Ford, B.,Nassar, N. (登録日: 2005-06-02, 公開日: 2006-03-14, 最終更新日: 2023-08-23)

主引用文献

Ford, B.,Hornak, V.,Kleinman, H.,Nassar, N.
Structure of a transient intermediate for GTP hydrolysis by ras.
Structure, 14:427-436, 2006

PubMed Abstract: The flexibility of the conserved 57DTAGQ61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the 57DTAGQ61 motif by mutating Gln61 to Gly. The crystal structure of the RasQ61G mutant reveals a new conformation of switch 2 that bears remarkable structural homology to an intermediate for GTP hydrolysis revealed by targeted molecular dynamics simulations. The mutation increased retention of GTP and inhibited Ras binding to the catalytic site, but not to the distal site of Sos. Most importantly, the thermodynamics of RafRBD binding to Ras are altered even though the structure of switch 1 is not affected by the mutation. Our results suggest that interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex even before the GDP conformation is reached.

PubMed: 16531227
DOI: 10.1016/j.str.2005.12.010

実験手法

X-RAY DIFFRACTION (2 Å)