The crystal structure of the heparin-binding reelin-N domain of f-spondin.
The extracellular matrix protein F-spondin mediates axon guidance during neuronal development. Its N-terminal domain, termed the reelin-N domain, is conserved in F-spondins, reelins, and other extracellular matrix proteins. In this study, a recombinant human reelin-N domain has been expressed, purified, and shown to bind heparin. The crystal structure of the reelin-N domain resolved to 2.0 A reveals a variant immunoglobulin-like fold and potential heparin-binding sites. Substantial conformational variations even in secondary structure are observed between the two chemically identical reelin-N domains in one crystallographic asymmetric unit. The variations may result from extensive, highly specific interactions across the interface of the two reelin-N domains. The calculated values of buried surface area and the interface's shape complementarity are consistent with the formation of a weak dimer. The homophilic asymmetric dimer can potentially offer advantages in binding to ligands such as glycosaminoglycans, which may, in turn, bridge the two reelin-N domains and stabilize the dimer.
Tan
Kemin
K
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ktan@anl.gov
Duquette
Mark
M
Liu
Jin-huan
JH
Lawler
Jack
J
Wang
Jia-huai
JH
D000595:Amino Acid Sequence; D001665:Binding Sites; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry*; D018360:Crystallography, X-Ray; D019281:Dimerization; D016326:Extracellular Matrix Proteins / Q000737:chemistry*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D000091042:Reelin Protein; D016415:Sequence Alignment; D012697:Serine Endopeptidases / Q000737:chemistry*; D013499:Surface Properties
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C429104:SPON1 protein, human; D006493:Heparin; C000717127:RELN protein, human; D012697:Serine Endopeptidases