Article
- The EMBO Journal (2003) 22, 1508 - 1517
- doi:10.1093/emboj/cdg150
Subject Category:
A novel cell binding site in the coiled-coil domain of laminin involved in capillary morphogenesis
Laura Sanz1,4, Laura García-Bermejo1,4, Francisco J. Blanco2, Peter Kristensen3, Mónica Feijóo1, Eduardo Suárez1, Belén Blanco1 and Luis Álvarez-Vallina1
- Department of Immunology, Hospital Universitario Clínica Puerta de Hierro, 28035 Madrid, Spain
- NMR Group, Centro Nacional de Investigaciones Oncológicas, 28029 Madrid, Spain
- Department of Molecular and Structural Biology, University of Aarhus, 8000 Aarhus C, Denmark
- L.Sanz and L.García-Bermejo contributed equally to this work
Correspondence to:
Luis Álvarez-Vallina, E-mail: lalvarezv.hpth@salud.madrid.org
Received 4 November 2002; Accepted 12 February 2003; Revised 6 February 2003
Abstract
Recently, we reported the isolation and characterization of an anti-laminin antibody that modulates the extracellular matrix-dependent morphogenesis of endothelial cells. Here we use this antibody to precisely map the binding site responsible for mediating this biologically important interaction. By using a phage display-assisted mapping strategy to preserve protein structure, we demonstrate for the first time that the coiled-coil region of laminin contains a cell binding site. The adhesion motif is formed by residues contributed by both 
and 
chains, and is located in the middle part of the rod-like portion in a highly flexible area, which corresponds to a protease-susceptible site. Based on this information, a peptide mimotope was used to characterize the cognate receptor. Although we can not rule out the implication of other receptors, our results demonstrate that the laminin helical rod active site interacts with 2
1 integrin on the surface of endothelial cells. These findings provide new insight into the complex mechanisms regulating capillary morphogenesis.
Keywords:
- coiled-coil,
- extracellular matrix,
- integrin,
- laminin
