1ryh
From Proteopedia
(New page: 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=" | + | |
caption="1ryh, resolution 1.75Å" /> | caption="1ryh, resolution 1.75Å" /> | ||
'''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 | + | 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:// | + | 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 | + | [[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:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:55:57 2008'' |
Revision as of 12:55, 21 February 2008
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Alternative Splicing of Rac1 Generates Rac1b, a Self-activating GTPase
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.
About this Structure
1RYH is a Single protein structure of sequence from Homo sapiens with and as ligands. Active as Small monomeric GTPase, with EC number 3.6.5.2 Full crystallographic information is available from OCA.
Reference
Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase., Fiegen D, Haeusler LC, Blumenstein L, Herbrand U, Dvorsky R, Vetter IR, Ahmadian MR, J Biol Chem. 2004 Feb 6;279(6):4743-9. Epub 2003 Nov 18. PMID:14625275
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