3t6p

From Proteopedia

(Difference between revisions)

Revision as of 16:45, 6 July 2022

IAP antagonist-induced conformational change in cIAP1 promotes E3 ligase activation via dimerization

Structural highlights

3t6p is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	API1, BIRC2, IAP2, MIHB, RNF48 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BIRC2_HUMAN] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.^[1] ^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Inhibitor of apoptosis (IAP) proteins are negative regulators of cell death. IAP family members contain RING domains that impart E3 ubiquitin ligase activity. Binding of endogenous or small-molecule antagonists to select baculovirus IAP repeat (BIR) domains within cellular IAP (cIAP) proteins promotes autoubiquitination and proteasomal degradation and so releases inhibition of apoptosis mediated by cIAP. Although the molecular details of antagonist-BIR domain interactions are well understood, it is not clear how this binding event influences the activity of the RING domain. Here biochemical and structural studies reveal that the unliganded, multidomain cIAP1 sequesters the RING domain within a compact, monomeric structure that prevents RING dimerization. Antagonist binding induces conformational rearrangements that enable RING dimerization and formation of the active E3 ligase.

Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination.,Dueber EC, Schoeffler AJ, Lingel A, Elliott JM, Fedorova AV, Giannetti AM, Zobel K, Maurer B, Varfolomeev E, Wu P, Wallweber HJ, Hymowitz SG, Deshayes K, Vucic D, Fairbrother WJ Science. 2011 Oct 21;334(6054):376-80. PMID:22021857^[6]

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

References

↑ Samuel T, Okada K, Hyer M, Welsh K, Zapata JM, Reed JC. cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. Cancer Res. 2005 Jan 1;65(1):210-8. PMID:15665297
↑ Xu L, Zhu J, Hu X, Zhu H, Kim HT, LaBaer J, Goldberg A, Yuan J. c-IAP1 cooperates with Myc by acting as a ubiquitin ligase for Mad1. Mol Cell. 2007 Dec 14;28(5):914-22. PMID:18082613 doi:10.1016/j.molcel.2007.10.027
↑ Broemer M, Tenev T, Rigbolt KT, Hempel S, Blagoev B, Silke J, Ditzel M, Meier P. Systematic in vivo RNAi analysis identifies IAPs as NEDD8-E3 ligases. Mol Cell. 2010 Dec 10;40(5):810-22. doi: 10.1016/j.molcel.2010.11.011. PMID:21145488 doi:10.1016/j.molcel.2010.11.011
↑ Cartier J, Berthelet J, Marivin A, Gemble S, Edmond V, Plenchette S, Lagrange B, Hammann A, Dupoux A, Delva L, Eymin B, Solary E, Dubrez L. Cellular inhibitor of apoptosis protein-1 (cIAP1) can regulate E2F1 transcription factor-mediated control of cyclin transcription. J Biol Chem. 2011 Jul 29;286(30):26406-17. doi: 10.1074/jbc.M110.191239. Epub, 2011 Jun 8. PMID:21653699 doi:10.1074/jbc.M110.191239
↑ Bertrand MJ, Lippens S, Staes A, Gilbert B, Roelandt R, De Medts J, Gevaert K, Declercq W, Vandenabeele P. cIAP1/2 are direct E3 ligases conjugating diverse types of ubiquitin chains to receptor interacting proteins kinases 1 to 4 (RIP1-4). PLoS One. 2011;6(9):e22356. doi: 10.1371/journal.pone.0022356. Epub 2011 Sep 12. PMID:21931591 doi:10.1371/journal.pone.0022356
↑ Dueber EC, Schoeffler AJ, Lingel A, Elliott JM, Fedorova AV, Giannetti AM, Zobel K, Maurer B, Varfolomeev E, Wu P, Wallweber HJ, Hymowitz SG, Deshayes K, Vucic D, Fairbrother WJ. Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science. 2011 Oct 21;334(6054):376-80. PMID:22021857 doi:10.1126/science.1207862

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/3t6p"

@@ Line 1: / Line 1: @@
 ==IAP antagonist-induced conformational change in cIAP1 promotes E3 ligase activation via dimerization==
-<StructureSection load='3t6p' size='340' side='right' caption='[[3t6p]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
+<StructureSection load='3t6p' size='340' side='right'caption='[[3t6p]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3t6p]] is a 1 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=3T6P OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3T6P FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3t6p]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3T6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3T6P FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">API1, BIRC2, IAP2, MIHB, RNF48 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">API1, BIRC2, IAP2, MIHB, RNF48 ([https://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3t6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t6p OCA], [http://pdbe.org/3t6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3t6p RCSB], [http://www.ebi.ac.uk/pdbsum/3t6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3t6p ProSAT]</span></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=3t6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3t6p OCA], [https://pdbe.org/3t6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3t6p RCSB], [https://www.ebi.ac.uk/pdbsum/3t6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3t6p ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/BIRC2_HUMAN BIRC2_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.<ref>PMID:15665297</ref> <ref>PMID:18082613</ref> <ref>PMID:21145488</ref> <ref>PMID:21653699</ref> <ref>PMID:21931591</ref>
+[[https://www.uniprot.org/uniprot/BIRC2_HUMAN BIRC2_HUMAN]] Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling, and cell proliferation, as well as cell invasion and metastasis. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle.<ref>PMID:15665297</ref> <ref>PMID:18082613</ref> <ref>PMID:21145488</ref> <ref>PMID:21653699</ref> <ref>PMID:21931591</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 19: / Line 19: @@
 </div>
 <div class="pdbe-citations 3t6p" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Baculoviral IAP repeat-containing protein|Baculoviral IAP repeat-containing protein]]
 == References ==
 <references/>
@@ Line 27: / Line 24: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Deshayes, K]]
 [[Category: Dueber, E C]]

3t6p

From Proteopedia

Revision as of 16:45, 6 July 2022

IAP antagonist-induced conformational change in cIAP1 promotes E3 ligase activation via dimerization

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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