Structural Organization of Human Full-Length PAR3 and the aPKC-PAR6 Complex

Mol Biotechnol. 2022 Dec;64(12):1319-1327. doi: 10.1007/s12033-022-00504-1. Epub 2022 May 24.

Abstract

The tripartite partition defect (PAR) polarity complex, which includes the proteins PAR3, atypical protein kinase C (aPKC), and PAR6, is a major regulator of cellular polarity. It is highly conserved and expressed in various tissues. Its largest component, PAR3, controls protein-protein interactions of the PAR complex with a variety of interaction partners, and PAR3 self-association is critical for the formation of filament-like structures. However, little is known about the structure of the PAR complex. Here, we purified non-filamentous PAR3 and the aPKC-PAR6 complex and characterized them by single-particle electron microscopy (EM). We expressed and purified an oligomerization-deficient form of PAR3, PAR3V13D,D70K, and the active aPKC-PAR6 dimer. For PAR3, engineering at two positions is sufficient to form stable single particles with a maximum dimension of 20 nm. aPKC-PAR6 forms a complex with a maximum dimension of 13.5 nm that contains single copies of aPKC. Thus, the data present a basis for further high-resolution studies of PAR proteins and PAR complex formation.

Keywords: PAR complex; PAR3; PAR6; Polarity; Single-particle electron microscopy; aPKC.

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Polarity
  • Humans
  • Protein Kinase C* / genetics
  • Protein Kinase C* / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • PARD6A protein, human
  • PKC-3 protein
  • Protein Kinase C