4kik

From Proteopedia

(Difference between revisions)

Current revision

Human IkB kinase beta

Structural highlights

4kik is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.83Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

IKKB_HUMAN Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Phosphorylation of inhibitor of nuclear transcription factor kappaB (IkappaB) by IkappaB kinase (IKK) triggers the degradation of IkappaB and migration of cytoplasmic kappaB to the nucleus where it promotes the transcription of its target genes. Activation of IKK is achieved by phosphorylation of its main subunit, IKKbeta, at the activation loop sites. Here, we report the 2.8 A resolution crystal structure of human IKKbeta (hIKKbeta), which is partially phosphorylated and bound to the staurosporine analog K252a. The hIKKbeta protomer adopts a trimodular structure that closely resembles that from Xenopus laevis (xIKKbeta): an N-terminal kinase domain (KD), a central ubiquitin-like domain (ULD), and a C-terminal scaffold/dimerization domain (SDD). Although hIKKbeta and xIKKbeta utilize a similar dimerization mode, their overall geometries are distinct. In contrast to the structure resembling closed shears reported previously for xIKKbeta, hIKKbeta exists as an open asymmetric dimer in which the two KDs are further apart, with one in an active and the other in an inactive conformation. Dimer interactions are limited to the C-terminal six-helix bundle that acts as a hinge between the two subunits. The observed domain movements in the structures of IKKbeta may represent trans-phosphorylation steps that accompany IKKbeta activation.

Crystal Structure of a Human IkappaB Kinase beta Asymmetric Dimer.,Liu S, Misquitta YR, Olland A, Johnson MA, Kelleher KS, Kriz R, Lin LL, Stahl M, Mosyak L J Biol Chem. 2013 Aug 2;288(31):22758-67. doi: 10.1074/jbc.M113.482596. Epub 2013, Jun 21. PMID:23792959^[7]

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

References

↑ Salmeron A, Janzen J, Soneji Y, Bump N, Kamens J, Allen H, Ley SC. Direct phosphorylation of NF-kappaB1 p105 by the IkappaB kinase complex on serine 927 is essential for signal-induced p105 proteolysis. J Biol Chem. 2001 Jun 22;276(25):22215-22. Epub 2001 Apr 10. PMID:11297557 doi:10.1074/jbc.M101754200
↑ Lobry C, Lopez T, Israel A, Weil R. Negative feedback loop in T cell activation through IkappaB kinase-induced phosphorylation and degradation of Bcl10. Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):908-13. Epub 2007 Jan 9. PMID:17213322 doi:10.1073/pnas.0606982104
↑ Cui J, Zhu L, Xia X, Wang HY, Legras X, Hong J, Ji J, Shen P, Zheng S, Chen ZJ, Wang RF. NLRC5 negatively regulates the NF-kappaB and type I interferon signaling pathways. Cell. 2010 Apr 30;141(3):483-96. doi: 10.1016/j.cell.2010.03.040. PMID:20434986 doi:10.1016/j.cell.2010.03.040
↑ Yoboua F, Martel A, Duval A, Mukawera E, Grandvaux N. Respiratory syncytial virus-mediated NF-kappa B p65 phosphorylation at serine 536 is dependent on RIG-I, TRAF6, and IKK beta. J Virol. 2010 Jul;84(14):7267-77. doi: 10.1128/JVI.00142-10. Epub 2010 Apr 21. PMID:20410276 doi:10.1128/JVI.00142-10
↑ Tsuchiya Y, Asano T, Nakayama K, Kato T Jr, Karin M, Kamata H. Nuclear IKKbeta is an adaptor protein for IkappaBalpha ubiquitination and degradation in UV-induced NF-kappaB activation. Mol Cell. 2010 Aug 27;39(4):570-82. doi: 10.1016/j.molcel.2010.07.030. PMID:20797629 doi:10.1016/j.molcel.2010.07.030
↑ Clark K, Peggie M, Plater L, Sorcek RJ, Young ER, Madwed JB, Hough J, McIver EG, Cohen P. Novel cross-talk within the IKK family controls innate immunity. Biochem J. 2011 Feb 15;434(1):93-104. doi: 10.1042/BJ20101701. PMID:21138416 doi:10.1042/BJ20101701
↑ Liu S, Misquitta YR, Olland A, Johnson MA, Kelleher KS, Kriz R, Lin LL, Stahl M, Mosyak L. Crystal Structure of a Human IkappaB Kinase beta Asymmetric Dimer. J Biol Chem. 2013 Aug 2;288(31):22758-67. doi: 10.1074/jbc.M113.482596. Epub 2013, Jun 21. PMID:23792959 doi:10.1074/jbc.M113.482596

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kik"

Categories: Homo sapiens | Large Structures | Liu S | Mosyak L

@@ Line 1: / Line 1: @@
 ==Human IkB kinase beta==
-<StructureSection load='4kik' size='340' side='right' caption='[[4kik]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
+<StructureSection load='4kik' size='340' side='right'caption='[[4kik]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4kik]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KIK OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KIK FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4kik]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KIK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KIK FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=KSA:K-252A'>KSA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.83&#8491;</td></tr>
-<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KSA:K-252A'>KSA</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IKBKB, IKKB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4kik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kik OCA], [https://pdbe.org/4kik PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4kik RCSB], [https://www.ebi.ac.uk/pdbsum/4kik PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4kik ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/I-kappa-B_kinase I-kappa-B kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.10 2.7.11.10] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4kik FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kik OCA], [http://pdbe.org/4kik PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4kik RCSB], [http://www.ebi.ac.uk/pdbsum/4kik PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4kik ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/IKKB_HUMAN IKKB_HUMAN]] Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.<ref>PMID:11297557</ref> <ref>PMID:17213322</ref> <ref>PMID:20434986</ref> <ref>PMID:20410276</ref> <ref>PMID:20797629</ref> <ref>PMID:21138416</ref>
+[https://www.uniprot.org/uniprot/IKKB_HUMAN IKKB_HUMAN] Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE. IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.<ref>PMID:11297557</ref> <ref>PMID:17213322</ref> <ref>PMID:20434986</ref> <ref>PMID:20410276</ref> <ref>PMID:20797629</ref> <ref>PMID:21138416</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 25: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: I-kappa-B kinase]]
+[[Category: Large Structures]]
-[[Category: Liu, S]]
+[[Category: Liu S]]
-[[Category: Mosyak, L]]
+[[Category: Mosyak L]]
-[[Category: Kinase]]
-[[Category: Nkb signaling]]
-[[Category: Transferase]]

4kik

From Proteopedia

Current revision

Human IkB kinase beta

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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