Structure of the C-terminal laminin G-like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-dystroglycan and heparin

EMBO J. 2000 Apr 3;19(7):1432-40. doi: 10.1093/emboj/19.7.1432.


The laminins are large heterotrimeric glycoproteins with fundamental roles in basement membrane architecture and function. The C-terminus of the laminin alpha chain contains a tandem of five laminin G-like (LG) domains. We report the 2.0 A crystal structure of the laminin alpha2 LG4-LG5 domain pair, which harbours binding sites for heparin and the cell surface receptor alpha-dystroglycan, and is 41% identical to the laminin alpha1 E3 fragment. LG4 and LG5 are arranged in a V-shaped fashion related by a 110 degrees rotation about an axis passing near the domain termini. An extended N-terminal segment is disulfide bonded to LG5 and stabilizes the domain pair. Two calcium ions, one each in LG4 and LG5, are located 65 A apart at the tips of the domains opposite the polypeptide termini. An extensive basic surface region between the calcium sites is proposed to bind alpha-dystroglycan and heparin. The LG4-LG5 structure was used to construct a model of the laminin LG1-LG5 tandem and interpret missense mutations underlying protein S deficiency.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites / genetics
  • Calcium / chemistry
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / metabolism
  • Dystroglycans
  • Heparin / metabolism
  • Humans
  • Laminin / chemistry*
  • Laminin / genetics
  • Laminin / metabolism
  • Ligands
  • Membrane Glycoproteins / metabolism
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation, Missense
  • Protein Conformation
  • Protein S Deficiency / genetics
  • Protein S Deficiency / metabolism
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Static Electricity


  • Cytoskeletal Proteins
  • DAG1 protein, human
  • Laminin
  • Ligands
  • Membrane Glycoproteins
  • laminin alpha 2
  • Dystroglycans
  • Heparin
  • Calcium