title: Olfactomedin-1 Has a V-shaped Disulfide-linked Tetrameric Structure.
abstract: Olfactomedin-1 (Olfm1; also known as noelin and pancortin) is a member of the olfactomedin domain-containing superfamily and a highly expressed neuronal glycoprotein important for nervous system development. It binds a number of secreted proteins and cell surface-bound receptors to induce cell signaling processes. Using a combined approach of x-ray crystallography, solution scattering, analytical ultracentrifugation, and electron microscopy we determined that full-length Olfm1 forms disulfide-linked tetramers with a distinctive V-shaped architecture. The base of the "V" is formed by two disulfide-linked dimeric N-terminal domains. Each of the two V legs consists of a parallel dimeric disulfide-linked coiled coil with a C-terminal β-propeller dimer at the tips. This agrees with our crystal structure of a C-terminal coiled-coil segment and β-propeller combination (Olfm1(coil-Olf)) that reveals a disulfide-linked dimeric arrangement with the β-propeller top faces in an outward exposed orientation. Similar to its family member myocilin, Olfm1 is stabilized by calcium. The dimer-of-dimers architecture suggests a role for Olfm1 in clustering receptors to regulate signaling and sheds light on the conformation of several other olfactomedin domain family members.
authors.affiliation: From the Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research and.
authors.forename: Matti F
authors.initials: MF
authors.lastname: Pronker
authors.affiliation: From the Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research and.
authors.forename: Trusanne G A A
authors.initials: TG
authors.lastname: Bos
authors.affiliation: Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Sharp
authors.affiliation: Van't Hoff Laboratory for Physical and Colloid Chemistry, Debye Institute of Nanomaterials Science, Department of Chemistry, Faculty of Science, Utrecht University, 3584 CH Utrecht, The Netherlands and.
authors.forename: Dominique M E
authors.initials: DM
authors.lastname: Thies-Weesie
authors.affiliation: From the Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research and b.j.c.janssen@uu.nl.
authors.forename: Bert J C
authors.initials: BJ
authors.lastname: Janssen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017386:Sequence Homology, Amino Acid
chemical_list: D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C081451:olfactomedin
keywords: analytical ultracentrifugation; cell signaling; coiled coil; development; disulfide; electron tomography; neurobiology; olfactomedin-1 (Olfm1); small angle x-ray scattering (SAXS); x-ray crystallography