4DC2

Structure of PKC in Complex with a Substrate Peptide from Par-3

Summary for 4DC2

• Entry DOI: 10.2210/pdb4dc2/pdb
• Descriptor: Protein kinase C iota type, Partitioning defective 3 homolog, ADENINE, ... (4 entities in total)
• Functional Keywords: kinase, substrate, cell polarity, par-3, atypical pkc, transferase-transferase substrate complex, transferase/transferase substrate
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm (By similarity): Q62074; Endomembrane system: Q9Z340
• Total number of polymer chains: 2
• Total formula weight: 49039.89

Authors

Shang, Y.,Wang, C.,Yu, J.,Zhang, M. (deposition date: 2012-01-17, release date: 2012-07-11, Last modification date: 2024-11-20)

Primary citation

Wang, C.,Shang, Y.,Yu, J.,Zhang, M.
Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKC iota in complex with a substrate peptide from Par-3
Structure, 20:791-801, 2012

PubMed Abstract: 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 PKCι in complex with a peptide from Par-3 at 2.4 Å. PKCι 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 PKCι/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 PKCι resembles its substrate sequence, directly binds to and inhibits the activity of the kinase.

PubMed: 22579248
DOI: 10.1016/j.str.2012.02.022

Experimental method

X-RAY DIFFRACTION (2.4 Å)