4dc2

Publication Abstract from PubMed

Protein kinase C (PKC) play critical roles in many cellular functions including differentiation, proliferation, growth, and survival. However, the molecular bases governing PKC's substrate recognitions remain poorly understood. Here we determined the structure of PKCiota in complex with a peptide from Par-3 at 2.4 A. PKCiota in the complex adopts catalytically competent, closed conformation without phosphorylation of Thr402 in the activation loop. The Par-3 peptide binds to an elongated groove formed by the N- and C-lobes of the kinase domain. The PKCiota/Par-3 complex structure, together with extensive biochemical studies, reveals a set of substrate recognition sites common to all PKC isozymes as well as a hydrophobic pocket unique to aPKC. A consensus aPKC's substrate recognition sequence pattern can be readily identified based on the complex structure. Finally, we demonstrate that the pseudosubstrate sequence of PKCiota resembles its substrate sequence, directly binds to and inhibits the activity of the kinase.

Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3.,Wang C, Shang Y, Yu J, Zhang M Structure. 2012 May 9;20(5):791-801. PMID:22579248^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.