Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5

Yoshinori Hirano, Sosuke Yoshinaga, Kenji Ogura, Masashi Yokochi, Yukiko Noda, Hideki Sumimoto, Fuyuhiko Inagaki

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)


Atypical protein kinase C (aPKC) has been implicated in several signaling pathways such as cell polarity, cell survival, and cell differentiation. In contrast to other PKCs, aPKC is unique in having the PB1 (Phox and Bem 1) domain in the N terminus. The aPKC PB1 domain binds with ZIP/p62, Par6, or MEK5 through a PB1-PB1 domain interaction that controls the localization of aPKC. Here, we determined the three-dimensional structure of the PB1 domain of PKCι by NMR and found that the PB1 domain adopts a ubiquitin fold. The OPCA (OPR, PC, and AID) motif inserted into the ubiquitin fold was presented as a ββα fold in which the side chains of conserved Asp residues were oriented to the same direction to form an acidic surface. This structural feature suggested that the acidic surface of the PKCι PB1 domain interacted with the basic surface of the target PB1 domains, and this was confirmed in the case of the PKCι-ZIP/p62 complex by mutational analysis. Interestingly, in the PKCι PB1 domain a conserved lysine residue was located on the side opposite to the OPCA motif-presenting surface, suggesting dual roles for the PKCι PB1 domain in that it could interact with either the conserved lysine residue or the acidic residues on the OPCA motif of the target PB1 domains.

Original languageEnglish
Pages (from-to)31883-31890
Number of pages8
JournalJournal of Biological Chemistry
Issue number30
Publication statusPublished - Jul 23 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5'. Together they form a unique fingerprint.

Cite this