Characterization of lipid binding specificities of dysferlin C2 domains reveals novel interactions with phosphoinositides

Biochemistry. 2009 Mar 24;48(11):2377-84. doi: 10.1021/bi802242r.

Abstract

Dysferlin is a type II transmembrane protein implicated in Ca(2+)-dependent sarcolemmal membrane repair. Dysferlin has seven C2 domains, which are lipid and protein binding modules. In this study, we sought to characterize the lipid binding specificity of dysferlin's seven C2 domains. Dysferlin's C2A domain was able to bind to phosphatidylserine (PS), phosphatidylinositol 4-phosphate [PtdIns(4)P], and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)] in a Ca(2+)-dependent fashion. The remainder of the C2 domains exhibited weaker and Ca(2+)-independent binding to PS and no significant binding to phosphoinositides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Calcium / chemistry
  • Calcium / metabolism
  • Dysferlin
  • Humans
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Muscle Proteins / chemistry*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Phosphatidylinositols / chemistry*
  • Phosphatidylinositols / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Sequence Alignment

Substances

  • DYSF protein, human
  • Dysferlin
  • Membrane Proteins
  • Muscle Proteins
  • Phosphatidylinositols
  • Calcium