2fju: Difference between revisions
New page: left|200px<br /> <applet load="2fju" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fju, resolution 2.20Å" /> '''Activated Rac1 boun... |
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[[Image:2fju.gif|left|200px]]<br /> | [[Image:2fju.gif|left|200px]]<br /><applet load="2fju" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2fju, resolution 2.20Å" /> | caption="2fju, resolution 2.20Å" /> | ||
'''Activated Rac1 bound to its effector phospholipase C beta 2'''<br /> | '''Activated Rac1 bound to its effector phospholipase C beta 2'''<br /> | ||
==Overview== | ==Overview== | ||
Although diverse signaling cascades require the coordinated regulation of | Although diverse signaling cascades require the coordinated regulation of heterotrimeric G proteins and small GTPases, these connections remain poorly understood. We present the crystal structure of the GTPase Rac1 bound to phospholipase C-beta2 (PLC-beta2), a classic effector of heterotrimeric G proteins. Rac1 engages the pleckstrin-homology (PH) domain of PLC-beta2 to optimize its orientation for substrate membranes. Gbetagamma also engages the PH domain to activate PLC-beta2, and these two activation events are compatible, leading to additive stimulation of phospholipase activity. In contrast to PLC-delta, the PH domain of PLC-beta2 cannot bind phosphoinositides, eliminating this mode of regulation. The structure of the Rac1-PLC-beta2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, and substitutions within PLC-beta2 abrogate its stimulation by Rac1 but not by Gbetagamma, allowing for functional dissection of this integral signaling node. | ||
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
2FJU 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, CA and GSP as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] Full crystallographic information is available from [http:// | 2FJU 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=CA:'>CA</scene> and <scene name='pdbligand=GSP:'>GSP</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Phosphoinositide_phospholipase_C Phosphoinositide phospholipase C], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.4.11 3.1.4.11] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FJU OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Phosphoinositide phospholipase C]] | [[Category: Phosphoinositide phospholipase C]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Harden, T | [[Category: Harden, T K.]] | ||
[[Category: Jezyk, M | [[Category: Jezyk, M R.]] | ||
[[Category: Snyder, J | [[Category: Snyder, J T.]] | ||
[[Category: Sondek, J.]] | [[Category: Sondek, J.]] | ||
[[Category: CA]] | [[Category: CA]] | ||
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[[Category: protein-protein complex]] | [[Category: protein-protein complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:22:06 2008'' | ||
Revision as of 15:22, 21 February 2008
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Activated Rac1 bound to its effector phospholipase C beta 2
Overview
Although diverse signaling cascades require the coordinated regulation of heterotrimeric G proteins and small GTPases, these connections remain poorly understood. We present the crystal structure of the GTPase Rac1 bound to phospholipase C-beta2 (PLC-beta2), a classic effector of heterotrimeric G proteins. Rac1 engages the pleckstrin-homology (PH) domain of PLC-beta2 to optimize its orientation for substrate membranes. Gbetagamma also engages the PH domain to activate PLC-beta2, and these two activation events are compatible, leading to additive stimulation of phospholipase activity. In contrast to PLC-delta, the PH domain of PLC-beta2 cannot bind phosphoinositides, eliminating this mode of regulation. The structure of the Rac1-PLC-beta2 complex reveals determinants that dictate selectivity of PLC-beta isozymes for Rac GTPases over other Rho-family GTPases, and substitutions within PLC-beta2 abrogate its stimulation by Rac1 but not by Gbetagamma, allowing for functional dissection of this integral signaling node.
Disease
Known disease associated with this structure: Platelet PLC beta-2 deficiency OMIM:[604114]
About this Structure
2FJU is a Protein complex structure of sequences from Homo sapiens with MG, CA and GSP as ligands. Active as Phosphoinositide phospholipase C, with EC number 3.1.4.11 Full crystallographic information is available from OCA.
Reference
Crystal structure of Rac1 bound to its effector phospholipase C-beta2., Jezyk MR, Snyder JT, Gershberg S, Worthylake DK, Harden TK, Sondek J, Nat Struct Mol Biol. 2006 Dec;13(12):1135-40. Epub 2006 Nov 19. PMID:17115053
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