Olfactomedin-1 has a V-shaped disulfide-linked tetrameric structure. [Protein Structure and Folding]

April 21st, 2015 by Pronker, M. F., Bos, T. G. A. A., Sharp, T. H., Thies-Weesie, D. M. E., Janssen, B. J. C.

Olfactomedin-1 (Olfm1; also known as noelin, 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 determine 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 at the tips a C-terminal β-propeller dimer. This agrees with our crystal structure of a C-terminal coiled-coil segment and β-propeller combination (Olfm1coil-Olf), which 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 informs on the conformation of several other olfactomedin domain family members.