5ik7 | pdb_00005ik7
Laminin A2LG45 I-form, Apo.
Structural highlights
Disease[LAMA2_MOUSE] Note=Defects in Lama2 are a cause of murine muscular dystrophy (dy2J). Function[LAMA2_MOUSE] Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components. Publication Abstract from PubMedDystroglycan is a highly glycosylated extracellular matrix receptor with essential functions in skeletal muscle and the nervous system. Reduced matrix binding by alpha-dystroglycan (alpha-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-beta1,3-xylose-alpha1,3-]n. Using a dual exoglycosidase digestion, we confirm that this polysaccharide is present on native alpha-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-alpha2 bound to a LARGE-synthesized oligosaccharide. A single glucuronic acid-beta1,3-xylose disaccharide repeat straddles a Ca2+ ion in the LG4 domain, with oxygen atoms from both sugars replacing Ca2+-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. Structural basis of laminin binding to the LARGE glycans on dystroglycan.,Briggs DC, Yoshida-Moriguchi T, Zheng T, Venzke D, Anderson ME, Strazzulli A, Moracci M, Yu L, Hohenester E, Campbell KP Nat Chem Biol. 2016 Aug 15. doi: 10.1038/nchembio.2146. PMID:27526028[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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