PDBsum entry 5ik5

Structural protein

PDB id: 5ik5

Contents

Protein chain

379 a.a.

Ligands

A2G-GAL

NAG-NAG

BDP-XYS-BDP-XYS

GOL ×6

4MU

Metals

_CA ×2

Waters ×460

PDB id:

5ik5

Name:

Structural protein

Title:

Laminin a2lg45 c-form, g6/7 bound.

Structure:

Laminin subunit alpha-2. Chain: a. Fragment: unp residues 2730-3118. Synonym: laminin m chain,laminin-12 subunit alpha,laminin-2 subunit alpha,laminin-4 subunit alpha,merosin heavy chain. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: lama2. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293.

Resolution:

1.39Å R-factor: 0.150 R-free: 0.177

Authors:

D.C.Briggs,E.Hohenester,K.P.Campbell

Key ref:

D.C.Briggs et al. (2016). Structural basis of laminin binding to the LARGE glycans on dystroglycan. Nat Chem Biol, 12, 810-814. PubMed id: 27526028 DOI: 10.1038/nchembio.2146

Date:

03-Mar-16 Release date: 10-Aug-16

Protein chain

Q60675  (LAMA2_MOUSE) -  Laminin subunit alpha-2 from Mus musculus

Seq: 3118 a.a.

Struc: 379 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1038/nchembio.2146

Nat Chem Biol 12:810-814 (2016)

PubMed id: 27526028

Structural basis of laminin binding to the LARGE glycans on dystroglycan.

D.C.Briggs, T.Yoshida-Moriguchi, T.Zheng, D.Venzke, M.E.Anderson, A.Strazzulli, M.Moracci, L.Yu, E.Hohenester, K.P.Campbell.

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.