2ns5
The conserved N-terminal domain of Par-3 adopts a novel PB1-like structure required for Par-3 oligomerization and apical membrane localization
Structural highlights
FunctionPARD3_RAT Adapter protein involved in asymmetrical cell division and cell polarization processes. Seems to play a central role in the formation of epithelial tight junctions. Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Targets the phosphatase PTEN to cell junctions.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. The Par-3 NTD adopts a PB1-like structure required for Par-3 oligomerization and membrane localization.,Feng W, Wu H, Chan LN, Zhang M EMBO J. 2007 Jun 6;26(11):2786-96. Epub 2007 May 3. PMID:17476308[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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