A 3D model of Reelin subrepeat regions predicts Reelin binding to carbohydrates.
Reelin is a large molecule of the extracellular matrix (ECM) which regulates neuronal positioning during the early stages of cortical development in vertebrate species. The Reelin molecule can be subdivided into a smaller N-terminal domain, showing homology with F-spondin, and a larger C-terminal region containing 8 EGF-like repeats. The localization of Reelin in the ECM, its large dimensions and the modular organization of its primary structure led us to suppose a structure of its modules similar to domains commonly found in ECM proteins such as Agrin, laminins and thrombospondins. We therefore performed a sequence alignment and molecular modeling analysis to study the three-dimensional fold of the Reelin subrepeat regions. Our analysis produces a tentative model of the core region of the Reelin subrepeat sequences and suggests the presence in this 3D model of structural features common to polysaccharide-binding modules which are often found on proteoglycans of the ECM. These findings provide a conceptual framework for further experiments aimed at testing the functions of the EGF-like repeat regions of Reelin.
Panteri
Roger
R
Laboratory of Developmental Neuroscience, Università Campus Bio-Medico, Via Longoni 83, 00155 Rome, Italy. R.Panteri@unicampus.it
Paiardini
Alessandro
A
Keller
Flavio
F
D000595:Amino Acid Sequence; D002241:Carbohydrates; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D000091042:Reelin Protein; D012091:Repetitive Sequences, Nucleic Acid; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*
D002241:Carbohydrates; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D000091042:Reelin Protein; C429104:SPON1 protein, human; C000717127:RELN protein, human; D012697:Serine Endopeptidases