Bipartite mechanism for laminin-integrin interactions: Identification of the integrin-binding site in LG domains of the laminin α chain

• Published in: Matrix biology 2020-05, Vol.87, p.66-76
• Main Authors: Taniguchi, Yukimasa, Takizawa, Mamoru, Li, Shaoliang, Sekiguchi, Kiyotoshi
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Animals; Basement membrane; Binding Sites; Cell adhesion; Humans; Integrin; Integrin beta Chains - chemistry; Integrin beta Chains - metabolism; Laminin; Laminin - chemistry; Laminin - metabolism; Metal ions; Mice; Models, Molecular; Multiprotein Complexes - chemistry; Multiprotein Complexes - metabolism; Protein Binding; Protein Conformation
• ISSN: 0945-053X; 1569-1802
• DOI: 10.1016/j.matbio.2019.10.005

Laminins are major cell-adhesive proteins consisting of α, β, and γ chains, in which the three C-terminal globular domains of the α chain (LMα/LG1–3) and the C-terminal tail region of the γ1 chain (LMγ1-tail) are required for binding to integrin. Despite the recent progress on the role of LMγ1-tail in coordinating the metal ion-dependent adhesion site of the integrin β subunit, the mechanism by which LMα/LG1–3 interacts with integrin remains to be elucidated. We found that basic residues on the bottom face of LMα5/LG2 are required for binding laminin-511 to α6β1 integrin. Intermolecular cysteine scanning assays demonstrated that the basic residues in LMα5/LG2 were in contact with the acidic residues within the laminin-binding X1 region of the integrin α subunit in the laminin-integrin complex. These results indicate that LMα5/LG2 interacts directly with the integrin α subunit and comprises a bipartite integrin binding site of laminin-511 with the LMγ1-tail. •Amino acid residues involved in integrin binding by laminin-511 were identified.•The residues are all basic and clustered on the bottom face of the LG2 domain of the laminin α5 chain.•The basic residues are in direct contact with acidic residues in the putative laminin-binding X1 region of integrin α6 and α7 subunits.•The basic residues in the α5 chain comprise a bipartite integrin-binding interface with a glutamate residue in the C-terminal tail of the γ1 chain.