Structural and functional analysis of the actin binding domain of plectin suggests alternative mechanisms for binding to F-actin and integrin beta4

Structure. 2003 Jun;11(6):615-25. doi: 10.1016/s0969-2126(03)00090-x.


Plectin is a widely expressed cytoskeletal linker. Here we report the crystal structure of the actin binding domain of plectin and show that this region is sufficient for interaction with F-actin or the cytoplasmic region of integrin alpha6beta4. The structure is formed by two calponin homology domains arranged in a closed conformation. We show that binding to F-actin induces a conformational change in plectin that is inhibited by an engineered interdomain disulfide bridge. A two-step induced fit mechanism involving binding and subsequent domain rearrangement is proposed. In contrast, interaction with integrin alpha6beta4 occurs in a closed conformation. Competitive binding of plectin to F-actin and integrin alpha6beta4 may rely on the observed alternative binding mechanisms and involve both allosteric and steric factors.

Publication types

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

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Humans
  • Integrin beta4 / metabolism*
  • Intermediate Filament Proteins / chemistry*
  • Intermediate Filament Proteins / genetics
  • Intermediate Filament Proteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Plectin
  • Protein Binding
  • Protein Conformation*
  • Sequence Alignment
  • Thermodynamics


  • Actins
  • Integrin beta4
  • Intermediate Filament Proteins
  • PLEC protein, human
  • Plectin

Associated data

  • PDB/1MB8