Ligand-binding specificities of laminin-binding integrins: a comprehensive survey of laminin-integrin interactions using recombinant alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4 integrins

Matrix Biol. 2006 Apr;25(3):189-97. doi: 10.1016/j.matbio.2005.12.001. Epub 2006 Jan 18.


The interactions of cells with basement membranes are primarily mediated via the engagement of laminins by a group of integrin family proteins, including integrins alpha3beta1, alpha6beta1, alpha7beta1 and alpha6beta4. To explore the ligand-binding specificities of these laminin-binding integrins, we produced these integrins, including two alpha7beta1 splice variants (alpha7X1beta1 and alpha7X2beta1), as soluble recombinant proteins and determined their binding specificities and affinities toward a panel of purified laminin isoforms containing distinct alpha chains. Among the five laminin-binding integrins investigated, alpha3beta1 and alpha6beta4 exhibited a clear specificity for laminin-332 (alpha3beta3gamma2) and laminin-511 (alpha5beta1gamma1)/521 (alpha5beta2gamma1), while integrin alpha6beta1 showed a broad specificity, binding to all laminin isoforms with a preference for laminin-111 (alpha1beta1gamma1), laminin-332 and laminin-511/521. The two alpha7beta1 variants were distinct from alpha3beta1, alpha6beta1 and alpha6beta4 in that they did not bind to laminin-332. alpha7X1beta1 bound to all laminins, except laminin-332, with a preference for laminin-211 (alpha2beta1gamma1)/221 (alpha2beta2gamma1) and laminin-511/521, while alpha7X2beta1 bound preferentially to laminin-111 and laminin-211/221. Laminin-511/521 was the most preferred ligand for all the laminin-binding integrins, except for alpha7X2beta1, whereas laminin-411 was the poorest ligand, capable of binding to alpha6beta1 and alpha7X1beta1 with only modest binding affinities. These comprehensive analyses of the interactions between laminin-binding integrins and a panel of laminins clearly demonstrate that the isoforms of both integrins and laminins differ in their binding specificities and affinities, and provide a molecular basis for better understanding of the adhesive interactions of cells with basement membranes of defined laminin compositions.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Integrin alpha3beta1 / genetics
  • Integrin alpha3beta1 / metabolism*
  • Integrin alpha6beta1 / genetics
  • Integrin alpha6beta1 / metabolism*
  • Integrin alpha6beta4 / genetics
  • Integrin alpha6beta4 / metabolism*
  • Integrins / genetics
  • Integrins / metabolism*
  • Laminin / genetics
  • Laminin / metabolism*
  • Ligands*
  • Mice
  • Molecular Sequence Data
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Subunits / genetics
  • Protein Subunits / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Integrin alpha3beta1
  • Integrin alpha6beta1
  • Integrin alpha6beta4
  • Integrins
  • Laminin
  • Ligands
  • Protein Isoforms
  • Protein Subunits
  • Recombinant Proteins
  • integrin alpha7beta1