1ry4: Difference between revisions
New page: left|200px<br /><applet load="1ry4" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ry4" /> '''NMR Structure of the CRIB-PDZ module of Par-... |
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[[Image:1ry4.jpg|left|200px]]<br /><applet load="1ry4" size=" | [[Image:1ry4.jpg|left|200px]]<br /><applet load="1ry4" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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'''NMR Structure of the CRIB-PDZ module of Par-6'''<br /> | '''NMR Structure of the CRIB-PDZ module of Par-6'''<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== | ||
1RY4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http:// | 1RY4 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RY4 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, B | [[Category: Volkman, B F.]] | ||
[[Category: cdc-42]] | [[Category: cdc-42]] | ||
[[Category: cell polarization]] | [[Category: cell polarization]] | ||
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[[Category: polarity adaptor complex]] | [[Category: polarity adaptor complex]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:55:54 2008'' | ||
Revision as of 12:55, 21 February 2008
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NMR Structure of the CRIB-PDZ module of Par-6
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
1RY4 is a Single protein structure of sequence from Drosophila melanogaster. 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
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