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Structural insights into the intrinsic self-assembly of Par-3 N-terminal domain.

Zhang Y, Wang W, Chen J, Zhang K, Gao F, Gao B, Zhang S, Dong M, Besenbacher F, Gong W, Zhang M, Sun F, Feng W
Structure 21 997-1006 (2013)
Cited: 19 times
EuropePMC logo PMID: 23643951

Abstract

Par-3, the central organizer of the Par-3/Par-6/atypical protein kinase C complex, is a multimodular scaffold protein that is essential for cell polarity establishment and maintenance. The N-terminal domain (NTD) of Par-3 is capable of self-association to form filament-like structures, although the underlying mechanism is poorly understood. Here, we determined the crystal structure of Par-3 NTD and solved the filament structure by cryoelectron microscopy. We found that an intrinsic "front-to-back" interaction mode is important for Par-3 NTD self-association and that both the lateral and longitudinal packing within the filament are mediated by electrostatic interactions. Disruptions of the lateral or longitudinal packing significantly impaired Par-3 NTD self-association and thereby impacted the Par-3-mediated epithelial polarization. We finally demonstrated that a Par-3 NTD-like domain from histidine ammonia-lyase also harbors a similar self-association capacity. This work unequivocally provides the structural basis for Par-3 NTD self-association and characterizes one type of protein domain that can self-assemble via electrostatic interactions.

Articles - 4i6p mentioned but not cited (2)

  1. Flexible torsion-angle noncrystallographic symmetry restraints for improved macromolecular structure refinement. Headd JJ, Echols N, Afonine PV, Moriarty NW, Gildea RJ, Adams PD. Acta Crystallogr D Biol Crystallogr 70 1346-1356 (2014)
  2. Design principles for selective polarization of PAR proteins by cortical flows. Illukkumbura R, Hirani N, Borrego-Pinto J, Bland T, Ng K, Hubatsch L, McQuade J, Endres RG, Goehring NW. J Cell Biol 222 e202209111 (2023)


Reviews citing this publication (9)

  1. The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity. Lang CF, Munro E. Development 144 3405-3416 (2017)
  2. Structural Features of Tight-Junction Proteins. Heinemann U, Schuetz A. Int J Mol Sci 20 E6020 (2019)
  3. Structural Biology of Nuclear Auxin Action. Dinesh DC, Villalobos LIAC, Abel S. Trends Plant Sci 21 302-316 (2016)
  4. PAR3-PAR6-atypical PKC polarity complex proteins in neuronal polarization. Hapak SM, Rothlin CV, Ghosh S. Cell Mol Life Sci 75 2735-2761 (2018)
  5. Protein clustering for cell polarity: Par-3 as a paradigm. Harris TJC. F1000Res 6 1620 (2017)
  6. Going with the flow: insights from Caenorhabditis elegans zygote polarization. Gubieda AG, Packer JR, Squires I, Martin J, Rodriguez J. Philos Trans R Soc Lond B Biol Sci 375 20190555 (2020)
  7. The polarity protein PARD3 and cancer. Atashrazm F, Ellis S. Oncogene 40 4245-4262 (2021)
  8. Dual Function of Par3 in Tumorigenesis. Lv T, Xu J, Yuan H, Wang J, Jiang X. Front Oncol 12 915957 (2022)
  9. The Roles of Par3, Par6, and aPKC Polarity Proteins in Normal Neurodevelopment and in Neurodegenerative and Neuropsychiatric Disorders. Zhang L, Wei X. J Neurosci 42 4774-4793 (2022)

Articles citing this publication (8)

  1. The selective autophagy receptor p62 forms a flexible filamentous helical scaffold. Ciuffa R, Lamark T, Tarafder AK, Guesdon A, Rybina S, Hagen WJ, Johansen T, Sachse C. Cell Rep 11 748-758 (2015)
  2. A Single-Cell Biochemistry Approach Reveals PAR Complex Dynamics during Cell Polarization. Dickinson DJ, Schwager F, Pintard L, Gotta M, Goldstein B. Dev Cell 42 416-434.e11 (2017)
  3. Reconstruction of Par-dependent polarity in apolar cells reveals a dynamic process of cortical polarization. Kono K, Yoshiura S, Fujita I, Okada Y, Shitamukai A, Shibata T, Matsuzaki F. Elife 8 e45559 (2019)
  4. Redundant regulation of localization and protein stability of DmPar3. Kullmann L, Krahn MP. Cell Mol Life Sci 75 3269-3282 (2018)
  5. Necl-4/Cadm4 recruits Par-3 to the Schwann cell adaxonal membrane. Meng X, Maurel P, Lam I, Heffernan C, Stiffler MA, McBeath G, Salzer JL. Glia 67 884-895 (2019)
  6. Par3 in chick lens placode development. Melo MO, Moraes Borges R, Yan CYI. Genesis 55 (2017)
  7. A protein self-assembly model guided by electrostatic and hydrophobic dipole moments. Mozo-Villarías A, Querol E. PLoS One 14 e0216253 (2019)
  8. Structural Organization of Human Full-Length PAR3 and the aPKC-PAR6 Complex. Le LTM, Drakulic S, Nyengaard JR, Golas MM, Sander B. Mol Biotechnol 64 1319-1327 (2022)


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