Article
- The EMBO Journal (2000) 19, 1432 - 1440
- doi:10.1093/emboj/19.7.1432
Structure of the C-terminal laminin G-like domain pair of the laminin 
2 chain harbouring binding sites for -dystroglycan and heparin
Dominic Tisi1, Jan F. Talts2,3, Rupert Timpl2 and Erhard Hohenester1,4
- Biophysics Section, Blackett Laboratory, Imperial College, London SW7 2BW, UK
- Abteilung Proteinchemie, Max-Planck-Institut für Biochemie, D-82152 Martinsried, Germany
- Present address: Department of Cell and Molecular Biology, Lund University, S-22100 Lund, Sweden
- Division of Medicine, Imperial College School of Medicine, London SW7 2AZ, UK
Correspondence to:
Erhard Hohenester, E-mail: e.hohenester@ic.ac.uk
Received 4 January 2000; Accepted 2 February 2000; Revised 2 February 2000
Abstract
The laminins are large heterotrimeric glycoproteins with fundamental roles in basement membrane architecture and function. The C-terminus of the laminin 
chain contains a tandem of five laminin G-like (LG) domains. We report the 2.0 Å crystal structure of the laminin 2 LG4–LG5 domain pair, which harbours binding sites for heparin and the cell surface receptor -dystroglycan, and is 41% identical to the laminin 1 E3 fragment. LG4 and LG5 are arranged in a V-shaped fashion related by a 110° 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 Å apart at the tips of the domains opposite the polypeptide termini. An extensive basic surface region between the calcium sites is proposed to bind -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.
Keywords:
- dystroglycan,
- extracellular matrix,
- laminin E3 fragment,
- X-ray crystallography
