The crystal structure of a laminin G-like module reveals the molecular basis of alpha-dystroglycan binding to laminins, perlecan, and agrin.
Laminin G-like (LG) modules in the extracellular matrix glycoproteins laminin, perlecan, and agrin mediate the binding to heparin and the cell surface receptor alpha-dystroglycan (alpha-DG). These interactions are crucial to basement membrane assembly, as well as muscle and nerve cell function. The crystal structure of the laminin alpha 2 chain LG5 module reveals a 14-stranded beta sandwich. A calcium ion is bound to one edge of the sandwich by conserved acidic residues and is surrounded by residues implicated in heparin and alpha-DG binding. A calcium-coordinated sulfate ion is suggested to mimic the binding of anionic oligosaccharides. The structure demonstrates a conserved function of the LG module in calcium-dependent lectin-like alpha-DG binding.
Hohenester
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Biophysics Section, Blackett Laboratory, Imperial College, London, United Kingdom. e.hohenester@ic.ac.uk
Tisi
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Talts
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Timpl
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D018171:Agrin / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D018360:Crystallography, X-Ray; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin / Q000378:metabolism; D006497:Heparan Sulfate / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007797:Laminin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011509:Proteoglycans / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D013431:Sulfates / Q000378:metabolism
D018171:Agrin; D002118:Calcium; D003598:Cytoskeletal Proteins; D049030:Dystroglycans; D019812:Heparan Sulfate Proteoglycans; D006493:Heparin; D006497:Heparan Sulfate; D007797:Laminin; D037102:Lectins; D008562:Membrane Glycoproteins; D011509:Proteoglycans; D013431:Sulfates; C483081:DAG1 protein, human; C102645:laminin alpha 2; C071927:perlecan