Journal article
Structure of a Transient Intermediate for GTP Hydrolysis by Ras
Structure (London), Vol.14(3), pp.427-436
2006
DOI: 10.1016/j.str.2005.12.010
PMID: 16531227
Abstract
The flexibility of the conserved
57DTAGQ
61 motif is essential for Ras proper cycling in response to growth factors. Here, we increase the flexibility of the
57DTAGQ
61 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.
Details
- Title: Subtitle
- Structure of a Transient Intermediate for GTP Hydrolysis by Ras
- Creators
- Bradley Ford - Department of Physiology and Biophysics, Basic Sciences Tower, Stony Brook University, Stony Brook, New York 11794Viktor Hornak - Center for Structural Biology, Stony Brook University, Stony Brook, New York 11794Holly Kleinman - Department of Physiology and Biophysics, Basic Sciences Tower, Stony Brook University, Stony Brook, New York 11794Nicolas Nassar - Department of Physiology and Biophysics, Basic Sciences Tower, Stony Brook University, Stony Brook, New York 11794
- Resource Type
- Journal article
- Publication Details
- Structure (London), Vol.14(3), pp.427-436
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.str.2005.12.010
- PMID
- 16531227
- ISSN
- 0969-2126
- eISSN
- 1878-4186
- Language
- English
- Date published
- 2006
- Academic Unit
- Pathology
- Record Identifier
- 9984047606402771
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