The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization.
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.
Feng
Wei
W
Department of Biochemistry, Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Kowloon, Hong Kong.
Wu
Hao
H
Chan
Ling-Nga
LN
Zhang
Mingjie
M
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000648:ultrastructure; D016764:Cell Polarity / Q000235:genetics*; D002850:Chromatography, Gel; D008565:Membrane Proteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D019906:Nuclear Magnetic Resonance, Biomolecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats
D002352:Carrier Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; C472451:Pard3 protein, rat