期刊
STRUCTURE
卷 14, 期 3, 页码 427-436出版社
CELL PRESS
DOI: 10.1016/j.str.2005.12.010
关键词
-
资金
- NIGMS NIH HHS [T32 GM008444] Funding Source: Medline
The flexibility of the conserved (57)DTAGQ(61) Motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the (57)DTAGQ(61) motif by mutating GIn61 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据