title: Structural characterization of the interactions between palladin and α-actinin.
abstract: The interaction between α-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 α-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 α-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 α-actinin and various ligands, which appears to require an α-helical motif containing four hydrophobic residues, common to many α-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 α-actinin binding.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Moriah R
authors.initials: MR
authors.lastname: Beck
authors.forename: Carol A
authors.initials: CA
authors.lastname: Otey
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Campbell
mesh_terms: D000185:Actinin / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism*; D020832:EF Hand Motifs; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: C401401:ACTN2 protein, human; D003598:Cytoskeletal Proteins; C412722:PALLD protein, human; D010750:Phosphoproteins; D000185:Actinin