1ryh: Difference between revisions

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New page: left|200px<br /> <applet load="1ryh" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ryh, resolution 1.75Å" /> '''Alternative Splicin...
 
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[[Image:1ryh.gif|left|200px]]<br />
[[Image:1ryh.gif|left|200px]]<br /><applet load="1ryh" size="350" color="white" frame="true" align="right" spinBox="true"  
<applet load="1ryh" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="1ryh, resolution 1.75&Aring;" />
caption="1ryh, resolution 1.75&Aring;" />
'''Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase'''<br />
'''Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase'''<br />


==Overview==
==Overview==
Rac1b was recently identified in malignant colorectal tumors as an, alternative splice variant of Rac1 containing a 19-amino acid insertion, next to the switch II region. The structures of Rac1b in the GDP- and the, GppNHp-bound forms, determined at a resolution of 1.75 A, reveal that the, insertion induces an open switch I conformation and a highly mobile switch, II. As a consequence, Rac1b has an accelerated GEF-independent GDP/GTP, exchange and an impaired GTP hydrolysis, which is restored partially by, GTPase-activating proteins. Interestingly, Rac1b is able to bind the, GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent, manner, suggesting that the insertion does not completely abolish effector, interaction. The presented study provides insights into the structural and, biochemical mechanism of a self-activating GTPase.
Rac1b was recently identified in malignant colorectal tumors as an alternative splice variant of Rac1 containing a 19-amino acid insertion next to the switch II region. The structures of Rac1b in the GDP- and the GppNHp-bound forms, determined at a resolution of 1.75 A, reveal that the insertion induces an open switch I conformation and a highly mobile switch II. As a consequence, Rac1b has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. Interestingly, Rac1b is able to bind the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction. The presented study provides insights into the structural and biochemical mechanism of a self-activating GTPase.


==About this Structure==
==About this Structure==
1RYH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with MG and GNP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1RYH OCA].  
1RYH is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=MG:'>MG</scene> and <scene name='pdbligand=GNP:'>GNP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Small_monomeric_GTPase Small monomeric GTPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.5.2 3.6.5.2] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RYH OCA].  


==Reference==
==Reference==
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[[Category: Single protein]]
[[Category: Single protein]]
[[Category: Small monomeric GTPase]]
[[Category: Small monomeric GTPase]]
[[Category: Ahmadian, M.R.]]
[[Category: Ahmadian, M R.]]
[[Category: Fiegen, D.]]
[[Category: Fiegen, D.]]
[[Category: GNP]]
[[Category: GNP]]
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[[Category: gtp binding]]
[[Category: gtp binding]]


''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 19:08:26 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:55:57 2008''