PMID: 21569239

 

    Legend: Sugar

Title : The structure of the Ca²+-binding, glycosylated F-spondin domain of F-spondin - A C2-domain variant in an extracellular matrix protein

Abstract :

1. 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
2. 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
3. The FS domain is found in F-spondins, mindins, M-spondin and amphiF-spondin
4. RESULTS: We present the crystal structure of human F-spondin FS domain at 1.95Å resolution
5. The structure reveals a Ca2 +-binding C2 domain variant with an 8-stranded antiparallel β-sandwich fold
6. Though the primary sequences of the FS domains of F-spondin and mindin are less than 36% identical, their overall structures are very similar
7. 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
8. The integrin-binding motif found in mindin is not conserved in the F-spondin FS domain
9. CONCLUSION: The structure of the F-spondin FS domain completes the structural studies of the multiple-domain ECM molecule
10. 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
11. The structural properties of the FS domain revealed in this study pave the way for further exploration into the functions of F-spondin