5IK5

Laminin A2LG45 C-form, G6/7 bound.

Summary for 5IK5

• Entry DOI: 10.2210/pdb5ik5/pdb
• Related: 5IK4
• Related PRD ID: PRD_900084
• Descriptor: Laminin subunit alpha-2, beta-D-galactopyranose-(1-3)-2-acetamido-2-deoxy-alpha-D-galactopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (8 entities in total)
• Functional Keywords: extracellular matrix, ligand binding, lg domain, structural protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 1
• Total formula weight: 44879.57

Authors

Briggs, D.C.,Hohenester, E.,Campbell, K.P. (deposition date: 2016-03-03, release date: 2016-08-10, Last modification date: 2024-01-10)

Primary citation

Briggs, D.C.,Yoshida-Moriguchi, T.,Zheng, T.,Venzke, D.,Anderson, M.E.,Strazzulli, A.,Moracci, M.,Yu, L.,Hohenester, E.,Campbell, K.P.
Structural basis of laminin binding to the LARGE glycans on dystroglycan.
Nat.Chem.Biol., 12:810-814, 2016

PubMed Abstract: 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.

PubMed: 27526028
DOI: 10.1038/nchembio.2146

Experimental method

X-RAY DIFFRACTION (1.39 Å)