Download MendeleyStructure of the C-Terminal Laminin G-Like Domain Pair of the Laminin Alpha 2 Chain Harbouring Binding Sites for Alpha-Dystroglycan and Heparin
Tisi, D., Talts, J.F., Timpl, R., Hohenester, E.(2000) EMBO J 19: 1432
- PubMed: 10747011
- DOI: https://doi.org/10.1093/emboj/19.7.1432
- Primary Citation of Related Structures:
1DYK - PubMed Abstract:
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.
Organizational Affiliation:
Abteilung Proteinchemie, Max-Planck-Institut f¨¹r Biochemie, D-82152 Martinsried, Germany.
