biostudies-literatureBeck MRNCI NIH HHSNIGMS NIH HHS712-25https://www.ebi.ac.uk/biostudies/studies/S-EPMC3226707biostudies-literatureUnknown413(3)The interaction between ?-actinin and palladin, two actin-cross-linking proteins, is essential for proper bidirectional targeting of these proteins. As a first step toward understanding the role of this complex in organizing cytoskeletal actin, we have characterized binding interactions between the EF-hand domain of ?-actinin (Act-EF34) and peptides derived from palladin and generated an NMR-derived structural model for the Act-EF34/palladin peptide complex. The critical binding site residues are similar to an ?-actinin binding motif previously suggested for the complex between Act-EF34 and titin Z-repeats. The structure-based model of the Act-EF34/palladin peptide complex expands our understanding of binding specificity between the scaffold protein ?-actinin and various ligands, which appears to require an ?-helical motif containing four hydrophobic residues, common to many ?-actinin ligands. We also provide evidence that the Family X mutation in palladin, associated with a highly penetrant form of pancreatic cancer, does not interfere with ?-actinin binding.Journal of molecular biologyStructural characterization of the interactions between palladin and ?-actinin.PMC3226707R01 GM081505R01 GM080568-02F32 CA1399265R01GM080568R01GM081505R01 GM080568-04F32 CA139926-01R01 GM080568R01 GM080568-03Otey CACampbell SLBeck MRfalseStructural characterization of the interactions between palladin and ?-actinin.The interaction between ?-actinin and palladin, two actin-cross-linking proteins, is essential for proper bidirectional targeting of these proteins. As a first step toward understanding the role of this complex in organizing cytoskeletal actin, we have characterized binding interactions between the EF-hand domain of ?-actinin (Act-EF34) and peptides derived from palladin and generated an NMR-derived structural model for the Act-EF34/palladin peptide complex. The critical binding site residues are similar to an ?-actinin binding motif previously suggested for the complex between Act-EF34 and titin Z-repeats. The structure-based model of the Act-EF34/palladin peptide complex expands our understanding of binding specificity between the scaffold protein ?-actinin and various ligands, which appears to require an ?-helical motif containing four hydrophobic residues, common to many ?-actinin ligands. We also provide evidence that the Family X mutation in palladin, associated with a highly penetrant form of pancreatic cancer, does not interfere with ?-actinin binding.2011-01-01T00:00:00Z2011 Oct2021-02-20T18:56:38Z2019-03-27T00:46:32ZS-EPMC32267072192551110.1016/j.jmb.2011.08.059