| Structural highlights
Disease
HOIL1_HUMAN Autoinflammatory syndrome with pyogenic bacterial infection and amylopectinosis.
Function
HOIL1_HUMAN E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, such as UBE2L3/UBCM4, and then transfers it to substrates. Functions as an E3 ligase for oxidized IREB2 and both heme and oxygen are necessary for IREB2 ubiquitination. Promotes ubiquitination of TAB2 and IRF3 and their degradation by the proteasome. Component of the LUBAC complex which conjugates linear ('Met-1'-linked) polyubiquitin chains to substrates and plays a key role in NF-kappa-B activation and regulation of inflammation. LUBAC conjugates linear polyubiquitin to IKBKG and RIPK1 and is involved in activation of the canonical NF-kappa-B and the JNK signaling pathways. Linear ubiquitination mediated by the LUBAC complex interferes with TNF-induced cell death and thereby prevents inflammation. LUBAC is proposed to be recruited to the TNF-R1 signaling complex (TNF-RSC) following polyubiquitination of TNF-RSC components by BIRC2 and/or BIRC3 and to conjugate linear polyubiquitin to IKBKG and possibly other components contributing to the stability of the complex. Together with FAM105B/otulin, the LUBAC complex regulates the canonical Wnt signaling during angiogenesis. Binds polyubiquitin of different linkage types.[1] [2] [3] [4] [5] [6] [7] [8] [9]
Publication Abstract from PubMed
The RING-between-RING (RBR) E3 ubiquitin ligase family in humans comprises 14 members and is defined by a two-step catalytic mechanism in which ubiquitin is first transferred from an E2 ubiquitin-conjugating enzyme to the RBR active site and then to the substrate. To define the core features of this catalytic mechanism, we here structurally and biochemically characterise the two RBRs HOIL-1 and RNF216. Crystal structures of both enzymes in their RBR/E2-Ub/Ub transthiolation complexes capturing the first catalytic step, together with complementary functional experiments, reveal the defining features of the RBR catalytic mechanism. RBRs catalyse ubiquitination via a conserved transthiolation complex structure that enables efficient E2-to-RBR ubiquitin transfer. Our data also highlight a conserved RBR allosteric activation mechanism by distinct ubiquitin linkages that suggests RBRs employ a feed-forward mechanism. We finally identify that the HOIL-1 RING2 domain contains an unusual Zn2/Cys6 binuclear cluster that is required for catalytic activity and substrate ubiquitination.
The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family.,Wang XS, Cotton TR, Trevelyan SJ, Richardson LW, Lee WT, Silke J, Lechtenberg BC Nat Commun. 2023 Jan 11;14(1):168. doi: 10.1038/s41467-023-35871-z. PMID:36631489[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yamanaka K, Ishikawa H, Megumi Y, Tokunaga F, Kanie M, Rouault TA, Morishima I, Minato N, Ishimori K, Iwai K. Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2. Nat Cell Biol. 2003 Apr;5(4):336-40. PMID:12629548 doi:https://dx.doi.org/10.1038/ncb952
- ↑ Kirisako T, Kamei K, Murata S, Kato M, Fukumoto H, Kanie M, Sano S, Tokunaga F, Tanaka K, Iwai K. A ubiquitin ligase complex assembles linear polyubiquitin chains. EMBO J. 2006 Oct 18;25(20):4877-87. Epub 2006 Sep 28. PMID:17006537 doi:10.1038/sj.emboj.7601360
- ↑ Tian Y, Zhang Y, Zhong B, Wang YY, Diao FC, Wang RP, Zhang M, Chen DY, Zhai ZH, Shu HB. RBCK1 negatively regulates tumor necrosis factor- and interleukin-1-triggered NF-kappaB activation by targeting TAB2/3 for degradation. J Biol Chem. 2007 Jun 8;282(23):16776-82. Epub 2007 Apr 20. PMID:17449468 doi:https://dx.doi.org/10.1074/jbc.M701913200
- ↑ Zhang M, Tian Y, Wang RP, Gao D, Zhang Y, Diao FC, Chen DY, Zhai ZH, Shu HB. Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3. Cell Res. 2008 Nov;18(11):1096-104. doi: 10.1038/cr.2008.277. PMID:18711448 doi:https://dx.doi.org/10.1038/cr.2008.277
- ↑ Haas TL, Emmerich CH, Gerlach B, Schmukle AC, Cordier SM, Rieser E, Feltham R, Vince J, Warnken U, Wenger T, Koschny R, Komander D, Silke J, Walczak H. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol Cell. 2009 Dec 11;36(5):831-44. doi: 10.1016/j.molcel.2009.10.013. PMID:20005846 doi:10.1016/j.molcel.2009.10.013
- ↑ Tokunaga F, Sakata S, Saeki Y, Satomi Y, Kirisako T, Kamei K, Nakagawa T, Kato M, Murata S, Yamaoka S, Yamamoto M, Akira S, Takao T, Tanaka K, Iwai K. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation. Nat Cell Biol. 2009 Feb;11(2):123-32. doi: 10.1038/ncb1821. Epub 2009 Jan 11. PMID:19136968 doi:10.1038/ncb1821
- ↑ Gerlach B, Cordier SM, Schmukle AC, Emmerich CH, Rieser E, Haas TL, Webb AI, Rickard JA, Anderton H, Wong WW, Nachbur U, Gangoda L, Warnken U, Purcell AW, Silke J, Walczak H. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature. 2011 Mar 31;471(7340):591-6. doi: 10.1038/nature09816. PMID:21455173 doi:10.1038/nature09816
- ↑ Tokunaga F, Nakagawa T, Nakahara M, Saeki Y, Taniguchi M, Sakata S, Tanaka K, Nakano H, Iwai K. SHARPIN is a component of the NF-kappaB-activating linear ubiquitin chain assembly complex. Nature. 2011 Mar 31;471(7340):633-6. doi: 10.1038/nature09815. PMID:21455180 doi:10.1038/nature09815
- ↑ Ikeda F, Deribe YL, Skanland SS, Stieglitz B, Grabbe C, Franz-Wachtel M, van Wijk SJ, Goswami P, Nagy V, Terzic J, Tokunaga F, Androulidaki A, Nakagawa T, Pasparakis M, Iwai K, Sundberg JP, Schaefer L, Rittinger K, Macek B, Dikic I. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature. 2011 Mar 31;471(7340):637-41. doi: 10.1038/nature09814. PMID:21455181 doi:10.1038/nature09814
- ↑ Wang XS, Cotton TR, Trevelyan SJ, Richardson LW, Lee WT, Silke J, Lechtenberg BC. The unifying catalytic mechanism of the RING-between-RING E3 ubiquitin ligase family. Nat Commun. 2023 Jan 11;14(1):168. doi: 10.1038/s41467-023-35871-z. PMID:36631489 doi:https://dx.doi.org/10.1038/s41467-023-35871-z
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