A 3D model of Reelin subrepeat regions predicts Reelin binding to carbohydrates

• Published in: Brain research 2006-10, Vol.1116 (1), p.222-230
• Main Authors: Panteri, Roger, Paiardini, Alessandro, Keller, Flavio
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Carbohydrate; Carbohydrates; Cell Adhesion Molecules, Neuronal - chemistry; Cell Adhesion Molecules, Neuronal - metabolism; Cell physiology; Extracellular Matrix Proteins - chemistry; Extracellular Matrix Proteins - metabolism; Fundamental and applied biological sciences. Psychology; Humans; Miscellaneous; Modeling; Models, Molecular; Molecular and cellular biology; Molecular Sequence Data; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - metabolism; Peptides - metabolism; Protein Binding; Protein Folding; Protein Structure, Secondary; Reelin; Repetitive Sequences, Nucleic Acid; Serine Endopeptidases - chemistry; Serine Endopeptidases - metabolism; Subrepeat; β-Sandwich
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.07.128

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.