# The Structure of the Ca$$^{2+}$$-binding, Glycosylated F-spondin Domain of F-spondin - A C2-Domain Variant in an Extracellular Matrix Protein

 Title: The Structure of the Ca$$^{2+}$$-binding, Glycosylated F-spondin Domain of F-spondin - A C2-Domain Variant in an Extracellular Matrix Protein Author: Tan, Kemin; Lawler, Jack William Note: Order does not necessarily reflect citation order of authors. Citation: Tan, Kemin, and Jack Lawler. 2011. The structure of the Ca$$^{2+}$$-binding, glycosylated F-spondin domain of F-spondin - A C2-domain variant in an extracellular matrix protein. BMC Structural Biology 11:22. Full Text & Related Files: 3117680.pdf (2.827Mb; PDF) Abstract: Background: F-spondin is a multi-domain extracellular matrix (ECM) protein and a contact-repellent molecule that directs axon outgrowth and cell migration during development. The reelin_N domain and the F-spondin domain (FS domain) comprise a proteolytic fragment that interacts with the cell membrane and guides the projection of commissural axons to floor plate. The FS domain is found in F-spondins, mindins, M-spondin and amphiF-spondin. Results: We present the crystal structure of human F-spondin FS domain at 1.95$$\{AA}$$ resolution. The structure reveals a Ca$$^{2+}$$-binding C2 domain variant with an 8-stranded antiparallel $$\beta$$-sandwich fold. Though the primary sequences of the FS domains of F-spondin and mindin are less than 36% identical, their overall structures are very similar. The unique feature of F-spondin FS domain is the presence of three disulfide bonds associated with the N- and C-termini of the domain and a highly conserved N-linked glycosylation site. The integrin-binding motif found in mindin is not conserved in the F-spondin FS domain. Conclusion: The structure of the F-spondin FS domain completes the structural studies of the multiple-domain ECM molecule. The homology of its core structure to a common Ca$$^{2+}$$- and lipid-binding C2 domain suggests that the F-spondin FS domain may be responsible for part of the membrane targeting of F-spondin in its regulation of axon development. The structural properties of the FS domain revealed in this study pave the way for further exploration into the functions of F-spondin. Published Version: doi://10.1186/1472-6807-11-22 Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3117680/pdf/ Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:7351764 Downloads of this work: