Structural mechanism of laminin recognition by integrin

Recognition of laminin by integrin receptors is central to the epithelial cell adhesion to basement membrane, but the structural background of this molecular interaction remained elusive. Here, we report the structures of the prototypic laminin receptor alpha 6 beta 1 integrin alone and in complex with three-chain laminin-511 fragment determined via crystallography and cryo-electron microscopy, respectively. The laminin-integrin interface is made up of several binding sites located on all five subunits, with the laminin gamma 1 chain C-terminal portion providing focal interaction using two carboxylate anchor points to bridge metal-ion dependent adhesion site of integrin beta 1 subunit and Asn189 of integrin alpha 6 subunit. Laminin alpha 5 chain also contributes to the affinity and specificity by making electrostatic interactions with large surface on the beta -propeller domain of alpha 6, part of which comprises an alternatively spliced X1 region. The propeller sheet corresponding to this region shows unusually high mobility, suggesting its unique role in ligand capture. Recognition of laminin by integrin receptors mediates epithelial cell adhesion to basement membrane. Here, the structures of the alpha 6 beta 1 integrin alone and in complex with three-chain laminin-511 fragment reveal the laminin-integrin interface in molecular detail.

Automated summary

Recognition of laminin by integrin receptors mediates epithelial cell adhesion to basement membrane. The interface between laminin and integrin is composed of multiple binding sites on different subunits, with the gamma 1 chain of laminin playing a key role in bridging interactions between integrin alpha 6 and beta 1 subunits. The alpha 5 chain of laminin also enhances affinity and specificity by electrostatic interactions with the beta -propeller domain of integrin alpha 6.