The Olfactomedin Domain from Gliomedin is a {beta}-Propeller with Unique Structural Properties [Neurobiology]

December 17th, 2014 by Han, H., Kursula, P.

All members of the olfactomedin (OLF) family have a conserved extracellular OLF domain, for which a structure has not been available. We present here the crystal structure of the OLF domain from gliomedin. Gliomedin is a protein expressed by Schwann cells in peripheral nerves, important for the formation of the nodes of Ranvier. Gliomedin interacts with neuronal cell adhesion molecules, such as neurofascin, but the structural details of the interaction are not known. The structure of the OLF domain presents a 5-bladed β-propeller fold, with unusual geometric properties. The symmetry of the structure is not 5-fold, but rather, reveals a twisted arrangement. The conserved top face of the gliomedin OLF domain is likely to be important for binding to neuronal ligands. Our results provide a structural basis for the functions of gliomedin in Schwann cells, enable the understanding of the role of the gliomedin OLF domain in autoimmune neuropathies, and unravel the locations of human disease-causing mutations in other OLF family members, including myocilin.

Periaxin and AHNAK nucleoprotein 2 form intertwined homodimers through domain swapping [Protein Structure and Folding]

March 27th, 2014 by Han, H., Kursula, P.

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.