2fju: Difference between revisions

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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"  
<applet load="2fju" size="450" color="white" frame="true" align="right" spinBox="true"  
caption="2fju, resolution 2.20&Aring;" />
caption="2fju, resolution 2.20&Aring;" />
'''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, 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.
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://ispc.weizmann.ac.il/oca-bin/ocashort?id=2FJU OCA].  
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.K.]]
[[Category: Harden, T K.]]
[[Category: Jezyk, M.R.]]
[[Category: Jezyk, M R.]]
[[Category: Snyder, J.T.]]
[[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]]


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