Bipartite mechanism for laminin-integrin interactions: Identification of the integrin-binding site in LG domains of the laminin α chain

Abstract

Laminins are major cell-adhesive proteins consisting of α, β, and γ chains, in which the three C-terminal globular domains of the α chain (LMα/LG1–3) and the C-terminal tail region of the γ1 chain (LMγ1-tail) are required for binding to integrin. Despite the recent progress on the role of LMγ1-tail in coordinating the metal ion-dependent adhesion site of the integrin β subunit, the mechanism by which LMα/LG1–3 interacts with integrin remains to be elucidated. We found that basic residues on the bottom face of LMα5/LG2 are required for binding laminin-511 to α6β1 integrin. Intermolecular cysteine scanning assays demonstrated that the basic residues in LMα5/LG2 were in contact with the acidic residues within the laminin-binding X1 region of the integrin α subunit in the laminin-integrin complex. These results indicate that LMα5/LG2 interacts directly with the integrin α subunit and comprises a bipartite integrin binding site of laminin-511 with the LMγ1-tail.