1ZW6

Crystal Structure of the GTP-bound form of RasQ61G

Summary for 1ZW6

• Entry DOI: 10.2210/pdb1zw6/pdb
• Related: 1LF0 1ZVQ 5P21
• Descriptor: Transforming protein p21/H-Ras-1, MAGNESIUM ION, CALCIUM ION, ... (5 entities in total)
• Functional Keywords: gtpase, gtp, ras, g-protein, oncoprotein
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side: P01112
• Total number of polymer chains: 1
• Total formula weight: 19495.38

Authors

Ford, B.,Hornak, V.,Kleinman, H.,Nassar, N. (deposition date: 2005-06-03, release date: 2006-03-14, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.5 Å)