Mechanistic basis for the recognition of laminin-511 by α6β1 integrin

Abstract

The Glu residue in the laminin γ-tail forms a bipartite integrin binding site with three globular domains of the α chain.

Abstract

Laminins regulate diverse cellular functions through interaction with integrins. Two regions of laminins—three laminin globular domains of the α chain (LG1–3) and the carboxyl-terminal tail of the γ chain (γ-tail)—are required for integrin binding, but it remains unclear how the γ-tail contributes to the binding. We determined the crystal structure of the integrin binding fragment of laminin-511, showing that the γ-tail extends to the bottom face of LG1–3. Electron microscopic imaging combined with biochemical analyses showed that integrin binds to the bottom face of LG1–3 with the γ1-tail apposed to the metal ion–dependent adhesion site (MIDAS) of integrin β1. These findings are consistent with a model in which the γ-tail coordinates the metal ion in the MIDAS through its Glu residue.