Binding of Crumbs to the Par-6 CRIB-PDZ Module Is Regulated by Cdc42. Biochemistry 2016 Mar 15;55(10):1455-61
Date
02/20/2016Pubmed ID
26894406Pubmed Central ID
PMC5433836DOI
10.1021/acs.biochem.5b01342Scopus ID
2-s2.0-84961825293 (requires institutional sign-in at Scopus site) 27 CitationsAbstract
Par-6 is a scaffold protein that organizes other proteins into a complex required to initiate and maintain cell polarity. Cdc42-GTP binds the CRIB module of Par-6 and alters the binding affinity of the adjoining PDZ domain. Allosteric regulation of the Par-6 PDZ domain was first demonstrated using a peptide identified in a screen of typical carboxyl-terminal ligands. Crumbs, a membrane protein that localizes a conserved polarity complex, was subsequently identified as a functional partner for Par-6 that likely interacts with the PDZ domain. Here we show by nuclear magnetic resonance that Par-6 binds a Crumbs carboxyl-terminal peptide and report the crystal structure of the PDZ-peptide complex. The Crumbs peptide binds Par-6 more tightly than the previously studied carboxyl peptide ligand and interacts with the CRIB-PDZ module in a Cdc42-dependent manner. The Crumbs:Par-6 crystal structure reveals specific PDZ-peptide contacts that contribute to its higher affinity and Cdc42-enhanced binding. Comparisons with existing structures suggest that multiple C-terminal Par-6 ligands respond to a common conformational switch that transmits the allosteric effects of GTPase binding.
Author List
Whitney DS, Peterson FC, Kittell AW, Egner JM, Prehoda KE, Volkman BFAuthors
Francis C. Peterson PhD Professor in the Biochemistry department at Medical College of WisconsinBrian F. Volkman PhD Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCrystallography, X-Ray
Drosophila Proteins
Drosophila melanogaster
GTP-Binding Proteins
Membrane Proteins
PDZ Domains
Protein Binding
Protein Kinase C
Protein Structure, Secondary
Protein Structure, Tertiary
