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PDBsum entry 5ik7
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Structural protein
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PDB id
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5ik7
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References listed in PDB file
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Key reference
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Title
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Structural basis of laminin binding to the large glycans on dystroglycan.
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Authors
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D.C.Briggs,
T.Yoshida-Moriguchi,
T.Zheng,
D.Venzke,
M.E.Anderson,
A.Strazzulli,
M.Moracci,
L.Yu,
E.Hohenester,
K.P.Campbell.
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Ref.
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Nat Chem Biol, 2016,
12,
810-814.
[DOI no: ]
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PubMed id
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Abstract
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Dystroglycan is a highly glycosylated extracellular matrix receptor with
essential functions in skeletal muscle and the nervous system. Reduced matrix
binding by α-dystroglycan (α-DG) due to perturbed glycosylation is a
pathological feature of several forms of muscular dystrophy.
Like-acetylglucosaminyltransferase (LARGE) synthesizes the matrix-binding
heteropolysaccharide [-glucuronic acid-β1,3-xylose-α1,3-]n. Using a dual
exoglycosidase digestion, we confirm that this polysaccharide is present on
native α-DG from skeletal muscle. The atomic details of matrix binding were
revealed by a high-resolution crystal structure of laminin-G-like (LG) domains 4
and 5 (LG4 and LG5) of laminin-α2 bound to a LARGE-synthesized oligosaccharide.
A single glucuronic acid-β1,3-xylose disaccharide repeat straddles a Ca(2+) ion
in the LG4 domain, with oxygen atoms from both sugars replacing Ca(2+)-bound
water molecules. The chelating binding mode accounts for the high affinity of
this protein-carbohydrate interaction. These results reveal a previously
uncharacterized mechanism of carbohydrate recognition and provide a structural
framework for elucidating the mechanisms underlying muscular dystrophy.
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