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2lc6
From Proteopedia
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==Solution structure of Par-6 Q144C/L164C== | ==Solution structure of Par-6 Q144C/L164C== | ||
| - | <StructureSection load='2lc6' size='340' side='right' caption='[[2lc6 | + | <StructureSection load='2lc6' size='340' side='right'caption='[[2lc6]]' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | [[2lc6]] is a 1 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[2lc6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LC6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2LC6 FirstGlance]. <br> |
| - | <b> | + | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2lc6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lc6 OCA], [https://pdbe.org/2lc6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2lc6 RCSB], [https://www.ebi.ac.uk/pdbsum/2lc6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2lc6 ProSAT]</span></td></tr> |
| - | < | + | </table> |
| - | <b>Resources:</b> <span class='plainlinks'>[ | + | == Function == |
| + | [https://www.uniprot.org/uniprot/O97111_DROME O97111_DROME] | ||
| + | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
Here, we report a novel mechanism of PDZ (PSD-95/Dlg/ZO-1) domain regulation that distorts a conserved element of PDZ ligand recognition. The polarity regulator Par-6 assembles a conserved multiprotein complex and is directly modulated by the Rho GTPase Cdc42. Cdc42 binds the adjacent Cdc42/Rac interactive binding (CRIB) and PDZ domains of Par-6, increasing C-terminal ligand binding affinity by 10-fold. By solving structures of the isolated PDZ domain and a disulfide-stabilized CRIB-PDZ, we detected a conformational switch that controls affinity by altering the configuration of the conserved "GLGF" loop. As a result, lysine 165 is displaced from the PDZ core by an adjacent hydrophobic residue, disrupting coordination of the PDZ ligand-binding cleft. Stabilization of the CRIB:PDZ interface restores K165 to its canonical location in the binding pocket. We conclude that a unique "dipeptide switch" in the Par-6 PDZ transmits a signal for allosteric activation to the ligand-binding pocket. | Here, we report a novel mechanism of PDZ (PSD-95/Dlg/ZO-1) domain regulation that distorts a conserved element of PDZ ligand recognition. The polarity regulator Par-6 assembles a conserved multiprotein complex and is directly modulated by the Rho GTPase Cdc42. Cdc42 binds the adjacent Cdc42/Rac interactive binding (CRIB) and PDZ domains of Par-6, increasing C-terminal ligand binding affinity by 10-fold. By solving structures of the isolated PDZ domain and a disulfide-stabilized CRIB-PDZ, we detected a conformational switch that controls affinity by altering the configuration of the conserved "GLGF" loop. As a result, lysine 165 is displaced from the PDZ core by an adjacent hydrophobic residue, disrupting coordination of the PDZ ligand-binding cleft. Stabilization of the CRIB:PDZ interface restores K165 to its canonical location in the binding pocket. We conclude that a unique "dipeptide switch" in the Par-6 PDZ transmits a signal for allosteric activation to the ligand-binding pocket. | ||
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A Conformational Switch in the CRIB-PDZ Module of Par-6.,Whitney DS, Peterson FC, Volkman BF Structure. 2011 Nov 9;19(11):1711-22. PMID:22078569<ref>PMID:22078569</ref> | A Conformational Switch in the CRIB-PDZ Module of Par-6.,Whitney DS, Peterson FC, Volkman BF Structure. 2011 Nov 9;19(11):1711-22. PMID:22078569<ref>PMID:22078569</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| + | </div> | ||
| + | <div class="pdbe-citations 2lc6" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Drosophila melanogaster]] | [[Category: Drosophila melanogaster]] | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Peterson FC]] |
| - | [[Category: | + | [[Category: Volkman BF]] |
| - | [[Category: | + | [[Category: Whitney DS]] |
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Current revision
Solution structure of Par-6 Q144C/L164C
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