Structural analysis of the plakin domain of bullous pemphigoid antigen1 (BPAG1) suggests that plakins are members of the spectrin superfamily

J Mol Biol. 2007 Feb 9;366(1):244-57. doi: 10.1016/j.jmb.2006.11.036. Epub 2006 Nov 11.


Bullous pemphigoid antigen 1 (BPAG1) is a member of the plakin family of proteins. The plakins are multi-domain proteins that have been shown to interact with microtubules, actin filaments and intermediate filaments, as well as proteins found in cellular junctions. These interactions are mediated through different domains on the plakins. The interactions between plakins and components of specialized cell junctions such as desmosomes and hemidesmosomes are mediated through the so-called plakin domain, which is a common feature of the plakins. We report the crystal structure of a stable fragment from BPAG1, residues 226-448, defined by limited proteolysis of the whole plakin domain. The structure, determined by single-wavelength anomalous diffraction phasing from a selenomethionine-substituted crystal at 3.0 A resolution, reveals a tandem pair of triple helical bundles closely related to spectrin repeats. Based on this structure and analysis of sequence conservation, we propose that the architecture of plakin domains is defined by two pairs of spectrin repeats interrupted by a putative Src-Homology 3 (SH3) domain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Crystallization
  • Crystallography, X-Ray
  • Cytoskeletal Proteins / chemistry*
  • Cytoskeletal Proteins / genetics
  • Dystonin
  • Humans
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Plakins / chemistry*
  • Plakins / genetics
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Spectrin / chemistry*
  • Structure-Activity Relationship


  • Carrier Proteins
  • Cytoskeletal Proteins
  • DST protein, human
  • Dystonin
  • Nerve Tissue Proteins
  • Plakins
  • Spectrin

Associated data

  • PDB/2IAK