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Title | Olfactomedin-1 Has a V-shaped Disulfide-linked Tetrameric Structure. |
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Journal, issue, pages | J Biol Chem, Vol. 290, Issue 24, Page 15092-15101, Year 2015 |
Publish date | Jun 12, 2015 |
Authors | Matti F Pronker / Trusanne G A A Bos / Thomas H Sharp / Dominique M E Thies-Weesie / Bert J C Janssen / |
PubMed 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 ...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. |
External links | J Biol Chem / PubMed:25903135 / PubMed Central |
Methods | SAS (X-ray synchrotron) / EM (tomography) / X-ray diffraction |
Resolution | 2.4 Å |
Structure data | SASDAS7: EMDB-2940: EMDB-2941: EMDB-2942: EMDB-2943: EMDB-2944: PDB-5amo: |
Chemicals | ChemComp-NAG: ChemComp-GOL: ChemComp-CL: ChemComp-HOH: |
Source |
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Keywords | SIGNALING PROTEIN / OLFM1 / DISULFIDE / NEUROBIOLOGY / DEVELOPMENT / AMPA RECEPTOR / BETA PROPELLER |