Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Agrin / chemistry
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Agrin / metabolism*
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Amino Acid Motifs
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Amino Acid Sequence
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Animals
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Binding Sites
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Calcium / metabolism
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Crystallography, X-Ray
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Cytoskeletal Proteins / metabolism*
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Dystroglycans
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Heparan Sulfate Proteoglycans*
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Heparin / metabolism
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Heparitin Sulfate / chemistry
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Heparitin Sulfate / metabolism*
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Humans
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Laminin / chemistry*
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Laminin / genetics
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Laminin / metabolism*
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Lectins / metabolism
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Membrane Glycoproteins / metabolism*
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Mice
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Models, Molecular
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Molecular Sequence Data
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Mutation / genetics
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Protein Binding
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Protein Structure, Secondary
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Proteoglycans / chemistry
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Proteoglycans / metabolism*
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Sequence Alignment
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Structure-Activity Relationship
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Sulfates / metabolism
Substances
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Agrin
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Cytoskeletal Proteins
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DAG1 protein, human
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Heparan Sulfate Proteoglycans
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Laminin
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Lectins
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Membrane Glycoproteins
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Proteoglycans
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Sulfates
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laminin alpha 2
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perlecan
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Dystroglycans
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Heparin
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Heparitin Sulfate
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Calcium