Mechanistic basis for the recognition of laminin-511 by a6b1 integrin

Laminins regulate diverse cellular functions through interaction with integrins. Two regions of laminins—three laminin globular domains of the a chain (LG1–3) and the carboxyl-terminal tail of the g chain (g-tail)—are required for integrin binding, but it remains unclear how the g-tail contributes to the binding. We determined the crystal structure of the integrin binding fragment of laminin-511, showing that the g-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 g1-tail apposed to the metal ion–dependent adhesion site (MIDAS) of integrin b1. These findings are consistent with a model in which the g-tail coordinates the metal ion in the MIDAS through its Glu residue. D o