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1rzx
From Proteopedia
(New page: 200px<br /><applet load="1rzx" size="450" color="white" frame="true" align="right" spinBox="true" caption="1rzx, resolution 2.1Å" /> '''Crystal Structure of ...) |
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| - | [[Image:1rzx.gif|left|200px]]<br /><applet load="1rzx" size=" | + | [[Image:1rzx.gif|left|200px]]<br /><applet load="1rzx" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1rzx, resolution 2.1Å" /> | caption="1rzx, resolution 2.1Å" /> | ||
'''Crystal Structure of a Par-6 PDZ-peptide Complex'''<br /> | '''Crystal Structure of a Par-6 PDZ-peptide Complex'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Regulation of protein interaction domains is required for cellular | + | Regulation of protein interaction domains is required for cellular signaling dynamics. Here, we show that the PDZ protein interaction domain from the cell polarity protein Par-6 is regulated by the Rho GTPase Cdc42. Cdc42 binds to a CRIB domain adjacent to the PDZ domain, increasing the affinity of the Par-6 PDZ for its carboxy-terminal ligand by approximately 13-fold. Par-6 PDZ regulation is required for function as mutational disruption of Cdc42-Par-6 PDZ coupling leads to inactivation of Par-6 in polarized MDCK epithelial cells. Structural analysis reveals that the free PDZ domain has several deviations from the canonical PDZ conformation that account for its low ligand affinity. Regulation results from a Cdc42-induced conformational transition in the CRIB-PDZ module that causes the PDZ to assume a canonical, high-affinity PDZ conformation. The coupled CRIB and PDZ architecture of Par-6 reveals how simple binding domains can be combined to yield complex regulation. |
==About this Structure== | ==About this Structure== | ||
| - | 1RZX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with ACE as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1RZX is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster] with <scene name='pdbligand=ACE:'>ACE</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RZX OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Penkert, R | + | [[Category: Penkert, R R.]] |
| - | [[Category: Peterson, F | + | [[Category: Peterson, F C.]] |
| - | [[Category: Prehoda, K | + | [[Category: Prehoda, K E.]] |
| - | [[Category: Volkman, F | + | [[Category: Volkman, F B.]] |
[[Category: ACE]] | [[Category: ACE]] | ||
[[Category: cell cycle]] | [[Category: cell cycle]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:56:22 2008'' |
Revision as of 12:56, 21 February 2008
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Crystal Structure of a Par-6 PDZ-peptide Complex
Overview
Regulation of protein interaction domains is required for cellular signaling dynamics. Here, we show that the PDZ protein interaction domain from the cell polarity protein Par-6 is regulated by the Rho GTPase Cdc42. Cdc42 binds to a CRIB domain adjacent to the PDZ domain, increasing the affinity of the Par-6 PDZ for its carboxy-terminal ligand by approximately 13-fold. Par-6 PDZ regulation is required for function as mutational disruption of Cdc42-Par-6 PDZ coupling leads to inactivation of Par-6 in polarized MDCK epithelial cells. Structural analysis reveals that the free PDZ domain has several deviations from the canonical PDZ conformation that account for its low ligand affinity. Regulation results from a Cdc42-induced conformational transition in the CRIB-PDZ module that causes the PDZ to assume a canonical, high-affinity PDZ conformation. The coupled CRIB and PDZ architecture of Par-6 reveals how simple binding domains can be combined to yield complex regulation.
About this Structure
1RZX is a Single protein structure of sequence from Drosophila melanogaster with as ligand. Full crystallographic information is available from OCA.
Reference
Cdc42 regulates the Par-6 PDZ domain through an allosteric CRIB-PDZ transition., Peterson FC, Penkert RR, Volkman BF, Prehoda KE, Mol Cell. 2004 Mar 12;13(5):665-76. PMID:15023337
Page seeded by OCA on Thu Feb 21 14:56:22 2008
