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

Sci Adv. 2017 Sep 1;3(9):e1701497. doi: 10.1126/sciadv.1701497. eCollection 2017 Sep.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Integrin alpha6beta1 / chemistry*
  • Integrin alpha6beta1 / genetics
  • Integrin alpha6beta1 / metabolism
  • Ions / chemistry
  • Laminin / chemistry*
  • Laminin / genetics
  • Laminin / metabolism
  • Metals / chemistry
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Recombinant Proteins
  • Structure-Activity Relationship

Substances

  • Integrin alpha6beta1
  • Ions
  • Laminin
  • Metals
  • Recombinant Proteins
  • laminin-511, human