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

Abstract

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.