title: Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping.
abstract: Periaxin (PRX) is an abundant protein in the peripheral nervous system, with an important role in myelination. PRX participates in large molecular complexes, most likely through the interactions of its N-terminal PSD-95/Discs-large/ZO-1 (PDZ)-like domain. We present the crystal structures of the PDZ-like domains from PRX and its homologue AHNAK nucleoprotein 2 (AHNAK2). The unique intertwined, domain-swapped dimers provide a structural basis for the homodimerization of both proteins. The core of the homodimer is formed by a 6-stranded antiparallel β sheet, with every other strand from a different chain. The AHNAK2 PDZ domain structure contains a bound class III ligand peptide. The binding pocket is preformed, and the peptide-PDZ interactions have unique aspects, including two salt bridges and weak recognition of the peptide C terminus. Tight homodimerization may be central to the scaffolding functions of PRX and AHNAK2 in molecular complexes linking the extracellular matrix to the cytoskeletal network.
authors.affiliation: From the Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland, the German Electron Synchrotron (DESY), 22607 Hamburg, Germany, and.
authors.forename: Huijong
authors.initials: H
authors.lastname: Han
authors.affiliation: From the Faculty of Biochemistry and Molecular Medicine and Biocenter Oulu, University of Oulu, 90014 Oulu, Finland, the German Electron Synchrotron (DESY), 22607 Hamburg, Germany, and the Department of Chemistry, University of Hamburg, 22607 Hamburg, Germany petri.kursula@oulu.fi.
authors.forename: Petri
authors.initials: P
authors.lastname: Kursula
mesh_terms: D018360:Crystallography, X-Ray; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009363:Neoplasm Proteins / Q000737:chemistry* / Q000378:metabolism; D054731:PDZ Domains; D010455:Peptides / Q000378:metabolism; D055503:Protein Multimerization; D055550:Protein Stability; D020836:Protein Structure, Quaternary
chemical_list: C075176:AHNAK protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D010455:Peptides; C086745:periaxin
keywords: Crystal Structure; Dimerization; Domain Swapping; Myelin; PDZ Domain; Protein Domains; Protein Structure; Protein-Protein Interactions; X-ray Scattering