The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization

EMBO J. 2007 Jun 6;26(11):2786-96. doi: 10.1038/sj.emboj.7601702. Epub 2007 May 3.


The evolutionarily conserved Par-3/Par-6/aPKC complex is essential for the establishment and maintenance of polarity of a wide range of cells. Both Par-3 and Par-6 are PDZ domain containing scaffold proteins capable of binding to polarity regulatory proteins. In addition to three PDZ domains, Par-3 also contains a conserved N-terminal oligomerization domain (NTD) that is essential for proper subapical membrane localization and consequently the functions of Par-3. The molecular basis of NTD-mediated Par-3 membrane localization is poorly understood. Here, we describe the structure of a monomeric form of the Par-3 NTD. Unexpectedly, the domain adopts a PB1-like fold with both type-I and type-II structural features. The Par-3 NTD oligomerizes into helical filaments via front-to-back interactions. We further demonstrate that the NTD-mediated membrane localization of Par-3 in MDCK cells is solely attributed to its oligomerization capacity. The data presented in this study suggest that the Par-3 NTD is likely to facilitate the assembly of higher-order Par-3/Par-6/aPKC complex with increased avidities in targeting the complex to the subapical membrane domain and in binding to other polarity-regulating proteins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / ultrastructure
  • Cell Polarity / genetics*
  • Chromatography, Gel
  • Membrane Proteins / metabolism*
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Models, Molecular*
  • Molecular Sequence Data
  • Multiprotein Complexes / metabolism*
  • Nerve Tissue Proteins
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Conformation
  • Protein Structure, Tertiary / genetics
  • Rats


  • Carrier Proteins
  • Membrane Proteins
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Pard3 protein, rat

Associated data

  • PDB/2NS5