1xd2
From Proteopedia
(New page: 200px<br /> <applet load="1xd2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xd2, resolution 2.70Å" /> '''Crystal Structure o...) |
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| - | [[Image:1xd2.gif|left|200px]]<br /> | + | [[Image:1xd2.gif|left|200px]]<br /><applet load="1xd2" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1xd2" size=" | + | |
caption="1xd2, resolution 2.70Å" /> | caption="1xd2, resolution 2.70Å" /> | ||
'''Crystal Structure of a ternary Ras:SOS:Ras*GDP complex'''<br /> | '''Crystal Structure of a ternary Ras:SOS:Ras*GDP complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The classical model for the activation of the nucleotide exchange factor | + | The classical model for the activation of the nucleotide exchange factor Son of sevenless (SOS) involves its recruitment to the membrane, where it engages Ras. The recent discovery that Ras*GTP is an allosteric activator of SOS indicated that the regulation of SOS is more complex than originally envisaged. We now present crystallographic and biochemical analyses of a construct of SOS that contains the Dbl homology-pleckstrin homology (DH-PH) and catalytic domains and show that the DH-PH unit blocks the allosteric binding site for Ras and suppresses the activity of SOS. SOS is dependent on Ras binding to the allosteric site for both a lower level of activity, which is a result of Ras*GDP binding, and maximal activity, which requires Ras*GTP. The action of the DH-PH unit gates a reciprocal interaction between Ras and SOS, in which Ras converts SOS from low to high activity forms as Ras*GDP is converted to Ras*GTP by SOS. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1XD2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG, PO4 and GDP as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1XD2 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene>, <scene name='pdbligand=PO4:'>PO4</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=1XD2 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Boykevisch, S.]] | [[Category: Boykevisch, S.]] | ||
[[Category: Kuriyan, J.]] | [[Category: Kuriyan, J.]] | ||
| - | [[Category: Soisson, S | + | [[Category: Soisson, S M.]] |
[[Category: Sondermann, H.]] | [[Category: Sondermann, H.]] | ||
| - | [[Category: Yang, S | + | [[Category: Yang, S S.]] |
[[Category: GDP]] | [[Category: GDP]] | ||
[[Category: MG]] | [[Category: MG]] | ||
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[[Category: ras:sos complex]] | [[Category: ras:sos complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:53:30 2008'' |
Revision as of 13:53, 21 February 2008
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Crystal Structure of a ternary Ras:SOS:Ras*GDP complex
Contents |
Overview
The classical model for the activation of the nucleotide exchange factor Son of sevenless (SOS) involves its recruitment to the membrane, where it engages Ras. The recent discovery that Ras*GTP is an allosteric activator of SOS indicated that the regulation of SOS is more complex than originally envisaged. We now present crystallographic and biochemical analyses of a construct of SOS that contains the Dbl homology-pleckstrin homology (DH-PH) and catalytic domains and show that the DH-PH unit blocks the allosteric binding site for Ras and suppresses the activity of SOS. SOS is dependent on Ras binding to the allosteric site for both a lower level of activity, which is a result of Ras*GDP binding, and maximal activity, which requires Ras*GTP. The action of the DH-PH unit gates a reciprocal interaction between Ras and SOS, in which Ras converts SOS from low to high activity forms as Ras*GDP is converted to Ras*GTP by SOS.
Disease
Known diseases associated with this structure: Bladder cancer, somatic OMIM:[190020], Costello syndrome OMIM:[190020], Fibromatosis, gingival OMIM:[182530], Noonan syndrome 4 OMIM:[182530], Thyroid carcinoma, follicular, somatic OMIM:[190020]
About this Structure
1XD2 is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Full crystallographic information is available from OCA.
Reference
Structural analysis of autoinhibition in the Ras activator Son of sevenless., Sondermann H, Soisson SM, Boykevisch S, Yang SS, Bar-Sagi D, Kuriyan J, Cell. 2004 Oct 29;119(3):393-405. PMID:15507210
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