Han Huijong, Kursula Petri
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.
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 Biomedicine, University of Bergen, N-5020 Bergen, Norway
J Biol Chem. 2015 Feb 6;290(6):3612-21. doi: 10.1074/jbc.M114.627547. Epub 2014 Dec 17.
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 five-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.
嗅觉介质（OLF）家族的所有成员都有一个保守的细胞外OLF结构域，其结构尚未可知。我们在此展示了神经胶质瘤介质中OLF结构域的晶体结构。神经胶质瘤介质是一种由外周神经中的施万细胞表达的蛋白质，对郎飞结的形成很重要。神经胶质瘤介质与神经元细胞粘附分子相互作用，如神经束蛋白，但相互作用的结构细节尚不清楚。OLF结构域的结构呈现出具有不寻常几何特性的五叶β-螺旋桨折叠。该结构的对称性不是五重对称，而是呈现出扭曲的排列。神经胶质瘤介质OLF结构域保守的顶面可能对与神经元配体的结合很重要。我们的结果为神经胶质瘤介质在施万细胞中的功能提供了结构基础，有助于理解神经胶质瘤介质OLF结构域在自身免疫性神经病中的作用，并揭示了包括肌纤蛋白在内的其他OLF家族成员中人类致病突变的位置。
