1X1R

Crystal structure of M-Ras in complex with GDP

Summary for 1X1R

• Entry DOI: 10.2210/pdb1x1r/pdb
• Related: 1X1S
• Descriptor: Ras-related protein M-Ras, MAGNESIUM ION, GUANOSINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: gtp-binding, signaling protein
• Biological source: Mus musculus (house mouse)
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): O08989
• Total number of polymer chains: 1
• Total formula weight: 20892.78

Authors

Ye, M.,Shima, F.,Muraoka, S.,Liao, J.,Okamoto, H.,Yamamoto, M.,Tamura, A.,Yagi, N.,Ueki, T.,Kataoka, T. (deposition date: 2005-04-12, release date: 2005-07-26, Last modification date: 2023-10-25)

Primary citation

Ye, M.,Shima, F.,Muraoka, S.,Liao, J.,Okamoto, H.,Yamamoto, M.,Tamura, A.,Yagi, N.,Ueki, T.,Kataoka, T.
Crystal Structure of M-Ras Reveals a GTP-bound "Off" State Conformation of Ras Family Small GTPases
J.Biol.Chem., 280:31267-31275, 2005

PubMed Abstract: Although some members of Ras family small GTPases, including M-Ras, share the primary structure of their effector regions with Ras, they exhibit vastly different binding properties to Ras effectors such as c-Raf-1. We have solved the crystal structure of M-Ras in the GDP-bound and guanosine 5'-(beta,gamma-imido)triphosphate (Gpp(NH)p)-bound forms. The overall structure of M-Ras resembles those of H-Ras and Rap2A, except that M-Ras-Gpp(NH)p exhibits a distinctive switch I conformation, which is caused by impaired intramolecular interactions between Thr-45 (corresponding to Thr-35 of H-Ras) of the effector region and the gamma-phosphate of Gpp(NH)p. Previous 31P NMR studies showed that H-Ras-Gpp(NH)p exists in two interconverting conformations, states 1 and 2. Whereas state 2 is a predominant form of H-Ras and corresponds to the "on" conformation found in the complex with effectors, state 1 is thought to represent the "off" conformation, whose tertiary structure remains unknown. 31P NMR analysis shows that free M-Ras-Gpp(NH)p predominantly assumes the state 1 conformation, which undergoes conformational transition to state 2 upon association with c-Raf-1. These results indicate that the solved structure of M-Ras-Gp-p(NH)p corresponds to the state 1 conformation. The predominance of state 1 in M-Ras is likely to account for its weak binding ability to the Ras effectors, suggesting the importance of the tertiary structure factor in small GTPase-effector interaction. Further, the first determination of the state 1 structure provides a molecular basis for developing novel anti-cancer drugs as compounds that hold Ras in the state 1 "off" conformation.

PubMed: 15994326
DOI: 10.1074/jbc.M505503200

Experimental method

X-RAY DIFFRACTION (1.3 Å)