Structure of a WW domain containing fragment of dystrophin in complex with beta-dystroglycan

Nat Struct Biol. 2000 Aug;7(8):634-8. doi: 10.1038/77923.


Dystrophin and beta-dystroglycan are components of the dystrophin-glycoprotein complex (DGC), a multimolecular assembly that spans the cell membrane and links the actin cytoskeleton to the extracellular basal lamina. Defects in the dystrophin gene are the cause of Duchenne and Becker muscular dystrophies. The C-terminal region of dystrophin binds the cytoplasmic tail of beta-dystroglycan, in part through the interaction of its WW domain with a proline-rich motif in the tail of beta-dystroglycan. Here we report the crystal structure of this portion of dystrophin in complex with the proline-rich binding site in beta-dystroglycan. The structure shows that the dystrophin WW domain is embedded in an adjacent helical region that contains two EF-hand-like domains. The beta-dystroglycan peptide binds a composite surface formed by the WW domain and one of these EF-hands. Additionally, the structure reveals striking similarities in the mechanisms of proline recognition employed by WW domains and SH3 domains.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / metabolism*
  • Dystroglycans
  • Dystrophin / chemistry*
  • Dystrophin / metabolism*
  • EF Hand Motifs
  • Humans
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Proline / metabolism
  • Protein Binding
  • Sequence Alignment
  • Substrate Specificity
  • Tryptophan / metabolism*
  • src Homology Domains


  • Cytoskeletal Proteins
  • DAG1 protein, human
  • Dystrophin
  • Membrane Glycoproteins
  • Peptide Fragments
  • Dystroglycans
  • Tryptophan
  • Proline

Associated data

  • PDB/1EG3
  • PDB/1EG4