4dc2

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

Structural highlights

4dc2 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
NonStd Res:
Gene:	Pkcl (Mus musculus)
Activity:	Protein kinase C, with EC number 2.7.11.13
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[PARD3_RAT] Adapter protein involved in asymmetrical cell division and cell polarization processes. Seems to play a central role in the formation of epithelial tight junctions. Association with PARD6B may prevent the interaction of PARD3 with F11R/JAM1, thereby preventing tight junction assembly. The PARD6-PARD3 complex links GTP-bound Rho small GTPases to atypical protein kinase C proteins. Required for establishment of neuronal polarity and normal axon formation in cultured hippocampal neurons (By similarity). Targets the phosphatase PTEN to cell junctions.^[1] ^[2]

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^[3]

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

References

↑ Wu H, Feng W, Chen J, Chan LN, Huang S, Zhang M. PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell. 2007 Dec 14;28(5):886-98. PMID:18082612 doi:10.1016/j.molcel.2007.10.028
↑ Feng W, Wu H, Chan LN, Zhang M. Par-3-mediated junctional localization of the lipid phosphatase PTEN is required for cell polarity establishment. J Biol Chem. 2008 Aug 22;283(34):23440-9. doi: 10.1074/jbc.M802482200. Epub 2008 , Jun 10. PMID:18550519 doi:10.1074/jbc.M802482200
↑ Wang C, Shang Y, Yu J, Zhang M. Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3. Structure. 2012 May 9;20(5):791-801. PMID:22579248 doi:10.1016/j.str.2012.02.022

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OCA

[1] Wu H, Feng W, Chen J, Chan LN, Huang S, Zhang M. PDZ domains of Par-3 as potential phosphoinositide signaling integrators. Mol Cell. 2007 Dec 14;28(5):886-98. PMID:18082612 doi:10.1016/j.molcel.2007.10.028

[2] Feng W, Wu H, Chan LN, Zhang M. Par-3-mediated junctional localization of the lipid phosphatase PTEN is required for cell polarity establishment. J Biol Chem. 2008 Aug 22;283(34):23440-9. doi: 10.1074/jbc.M802482200. Epub 2008 , Jun 10. PMID:18550519 doi:10.1074/jbc.M802482200

[3] Wang C, Shang Y, Yu J, Zhang M. Substrate recognition mechanism of atypical protein kinase Cs revealed by the structure of PKCiota in complex with a substrate peptide from Par-3. Structure. 2012 May 9;20(5):791-801. PMID:22579248 doi:10.1016/j.str.2012.02.022

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