Structure and function of laminin LG modules.
Laminin G domain-like (LG) modules of approximately 180-200 residues are found in a number of extracellular and receptor proteins and often are present in tandem arrays. LG modules are implicated in interactions with cellular receptors (integrins, alpha-dystroglycan), sulfated carbohydrates and other extracellular ligands. The recently determined crystal structures of LG modules of the laminin alpha2 chain reveal a compact beta sandwich fold and identify a novel calcium binding site. Binding epitopes for heparin, sulfatides and alpha-dystroglycan have been mapped by site-directed mutagenesis and show considerable overlap. The epitopes are located in surface loops around the calcium site, which in other proteins (agrin, neurexins) are modified by alternative splicing. Efficient ligand binding often requires LG modules to be present in tandem. The close proximity of the N- and C-termini in the LG module, as well as a unique link region between laminin LG3 and LG4, impose certain constraints on the arrangement of LG tandems. Further modifications may be introduced by proteolytic processing of laminin G domains, which is known to occur in the alpha2, alpha3 and alpha4 chains.
Timpl
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Max-Planck-Institut für Biochemie, Am Klopferspitz 18a, D-82152, Martinsried, Germany. timpl@biochem.mpg.de
Tisi
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Talts
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Andac
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Sasaki
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Hohenester
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D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013329:Structure-Activity Relationship; D013433:Sulfoglycosphingolipids / Q000378:metabolism
D007797:Laminin; D011506:Proteins; D011956:Receptors, Cell Surface; D013433:Sulfoglycosphingolipids; D006493:Heparin; D010450:Endopeptidases