View source for 4mjs


==crystal structure of a PB1 complex==
<StructureSection load='4mjs' size='340' side='right'caption='[[4mjs]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4mjs]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MJS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MJS FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4mjs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mjs OCA], [https://pdbe.org/4mjs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mjs RCSB], [https://www.ebi.ac.uk/pdbsum/4mjs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mjs ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KPCZ_RAT KPCZ_RAT] Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukins production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In NF-kappa-B-mediated inflammatory response, can relieve the SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Is necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells.<ref>PMID:8378304</ref> <ref>PMID:8557035</ref> <ref>PMID:9374484</ref> <ref>PMID:9177193</ref> <ref>PMID:10022904</ref> <ref>PMID:10747026</ref> <ref>PMID:11525734</ref> <ref>PMID:11158308</ref> <ref>PMID:11914719</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The atypical PKC isoforms (zeta and i) play essential roles in regulating various cellular processes. Both the hetero-interaction between PKCzeta and p62 through their N-terminal PB1 domains and the homo-oligomerization of p62 via its PB1 domain are critical for the activation of NF-kappaB signaling; however, the molecular mechanisms concerning the formation and regulation of these homotypic complexes remain unclear. Here we determined the crystal structure of PKCzeta-PB1 in complex with a monomeric p62-PB1 mutant, where the massive electrostatic interactions between the acidic OPCA motif of PKCzeta-PB1 and the basic surface of p62-PB1, as well as additional hydrogen bonds, ensure the formation of a stable and specific complex. The PKCzeta-p62 interaction is interfered with the modification of a specific Cys of PKCzeta by the antiarthritis drug aurothiomalate, though all four cysteine residues in the PKCzeta-PB1 domain can be modified in in vitro assay. In addition, detailed structural and biochemical analyses demonstrate that the PB1 domains of aPKCs belong to the type I group, which can depolymerize the high-molecular-weight p62 aggregates into homo-oligomers of lower order. These data together unravel the molecular mechanisms of the homo-or hetero-interactions between p62 and PKCzeta and provide the basis for designing inhibitors of NF-kappaB signaling.

Structural and biochemical insights into the homotypic PB1-PB1 complex between PKCzeta and p62.,Ren J, Wang J, Wang Z, Wu J Sci China Life Sci. 2014 Jan;57(1):69-80. doi: 10.1007/s11427-013-4592-z. Epub, 2013 Dec 26. PMID:24369353<ref>PMID:24369353</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4mjs" style="background-color:#fffaf0;"></div>

==See Also==
*[[Protein kinase C 3D structures|Protein kinase C 3D structures]]
*[[Sequestosome|Sequestosome]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Ren J]]
[[Category: Wang ZX]]
[[Category: Wu JW]]