title: The structure of the Ca²+-binding, glycosylated F-spondin domain of F-spondin - A C2-domain variant in an extracellular matrix protein.
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 1.95Å resolution. The structure reveals a Ca2+-binding C2 domain variant with an 8-stranded antiparallel β-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.
  
  
  CONCLUSIONS
  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 Ca2+- 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.
authors.affiliation: Midwest Center for Structural Genomics and Structural Biology Center, Biosciences Division, Argonne National Laboratory, Argonne, IL 60439, USA. ktan@anl.gov
authors.forename: Kemin
authors.initials: K
authors.lastname: Tan
authors.forename: Jack
authors.initials: J
authors.lastname: Lawler
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004220:Disulfides; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006031:Glycosylation; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D000091042:Reelin Protein; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D004220:Disulfides; D016326:Extracellular Matrix Proteins; D000091042:Reelin Protein; C429104:SPON1 protein, human; C000717127:RELN protein, human; D002118:Calcium