2fju
From Proteopedia
(New page: 200px<br /> <applet load="2fju" size="450" color="white" frame="true" align="right" spinBox="true" caption="2fju, resolution 2.20Å" /> '''Activated Rac1 boun...) |
|||
| Line 1: | Line 1: | ||
| - | [[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" |
| - | <applet load="2fju" size=" | + | |
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== | ||
| Line 11: | Line 10: | ||
==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== | ||
| Line 18: | Line 17: | ||
[[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]] | ||
| Line 27: | Line 26: | ||
[[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
|
Activated Rac1 bound to its effector phospholipase C beta 2
Contents |
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 , and 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
Page seeded by OCA on Thu Feb 21 17:22:06 2008
