Structure of the F-spondin reeler domain reveals a unique beta-sandwich fold with a deformable disulfide-bonded loop.
F-spondin is a secreted and extracellular matrix-attached protein that has been implicated in axonal pathfinding during neural development as well as in vascular remodelling in adult tissues. F-spondin is composed of a reeler, a spondin and six thrombospondin type 1 repeat domains. The reeler domain shares homology with the amino-terminal domain of reelin, a large secreted glycoprotein that guides migrating neurons during cortical development. Crystal structures of the F-spondin reeler domain were determined at 1.45 and 2.70 A resolution. The structure revealed a nine-stranded antiparallel beta-sandwich fold similar to the immunoglobulin or fibronectin type III domains, but with a unique extra beta-hairpin. Moreover, an amino-terminal extension which is anchored at its beginning via a conserved disulfide bond loosely packs against one face of the beta-sandwich, making a major contribution to the surface features of the domain. Structural comparison among the different molecules contained in two different crystals reveals an unusual conformational plasticity of the amino-terminal loop, suggesting its role in molecular interactions.
Nagae
Masamichi
M
Laboratory of Protein Synthesis and Expression, Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nishikawa
Ken
K
Yasui
Norihisa
N
Yamasaki
Motoo
M
Nogi
Terukazu
T
Takagi
Junichi
J
D000595:Amino Acid Sequence; D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D055029:Inverted Repeat Sequences / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics*; D000091042:Reelin Protein; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
D015816:Cell Adhesion Molecules, Neuronal; D004220:Disulfides; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C429104:SPON1 protein, human; C000717127:RELN protein, human; D012697:Serine Endopeptidases