1x1r
From Proteopedia
(New page: 200px<br /><applet load="1x1r" size="450" color="white" frame="true" align="right" spinBox="true" caption="1x1r, resolution 1.30Å" /> '''Crystal structure of...) |
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| - | [[Image:1x1r.gif|left|200px]]<br /><applet load="1x1r" size=" | + | [[Image:1x1r.gif|left|200px]]<br /><applet load="1x1r" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1x1r, resolution 1.30Å" /> | caption="1x1r, resolution 1.30Å" /> | ||
'''Crystal structure of M-Ras in complex with GDP'''<br /> | '''Crystal structure of M-Ras in complex with GDP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Although some members of Ras family small GTPases, including M-Ras, share | + | 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. |
==About this Structure== | ==About this Structure== | ||
| - | 1X1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MG and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1X1R is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GDP:'>GDP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X1R OCA]. |
==Reference== | ==Reference== | ||
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[[Category: gtp-binding]] | [[Category: gtp-binding]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:50:12 2008'' |
Revision as of 13:50, 21 February 2008
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Crystal structure of M-Ras in complex with GDP
Overview
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.
About this Structure
1X1R is a Single protein structure of sequence from Mus musculus with and as ligands. Full crystallographic information is available from OCA.
Reference
Crystal structure of M-Ras reveals a GTP-bound "off" state conformation of Ras family small GTPases., Ye M, Shima F, Muraoka S, Liao J, Okamoto H, Yamamoto M, Tamura A, Yagi N, Ueki T, Kataoka T, J Biol Chem. 2005 Sep 2;280(35):31267-75. Epub 2005 Jun 30. PMID:15994326
Page seeded by OCA on Thu Feb 21 15:50:12 2008
Categories: Mus musculus | Single protein | Kataoka, T. | Liao, J. | Muraoka, S. | Okamoto, H. | Shima, F. | Tamura, A. | Ueki, T. | Yagi, N. | Yamamoto, M. | Ye, M. | GDP | MG | Gtp-binding
