Olfactomedin-1 Has a V-shaped Disulfide-linked Tetrameric Structure |
| |
Authors: | Matti F Pronker Trusanne G A A Bos Thomas H Sharp Dominique M E Thies-Weesie Bert J C Janssen |
| |
Institution: | From the ‡Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research and ;¶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 ;§Section Electron Microscopy, Department of Molecular Cell Biology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands |
| |
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 (Olfm1coil-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. |
| |
Keywords: | cell signaling development disulfide electron tomography neurobiology small angle x-ray scattering (SAXS) x-ray crystallography olfactomedin-1 (Olfm1) analytical ultracentrifugation coiled coil |
|
|