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Research Article

o-Vanillin binds covalently to MAL/TIRAP Lys-210 but independently inhibits TLR2

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Article: 2313055 | Received 11 Aug 2023, Accepted 28 Jan 2024, Published online: 28 Feb 2024

References

  • Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1(2):1–15.
  • Ve T, Gay NJ, Mansell A, Kobe B, Kellie S. Adaptors in Toll-like receptor signaling and their potential as therapeutic targets. Curr Drug Targets. 2012;13(11):1360–1374.
  • Nimma S, Gu W, Maruta N, Li Y, Pan M, Saikot FK, Lim BYJ, McGuinness HY, Zaoti ZF, Li S, et al. Structural evolution of TIR-domain signalosomes. Front Immunol. 2021;12:784484.
  • O’Neill LAJ, Bryant CE, Doyle SL. Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 2009;61(2):177–197.
  • Gao W, Xiong Y, Li Q, Yang H. Inhibition of Toll-like receptor signaling as a promising therapy for inflammatory diseases: a journey from molecular to nano therapeutics. Front Physiol. 2017;8:508.
  • Roger T, Froidevaux C, Le Roy D, Reymond MK, Chanson AL, Mauri D, Burns K, Riederer BM, Akira S, Calandra T. Protection from lethal Gram-negative bacterial sepsis by targeting Toll-like receptor 4. Proc Natl Acad Sci USA. 2009;106(7):2348–2352.
  • Ding Y, Subramanian S, Montes VN, Goodspeed L, Wang S, Han C, Teresa AS, 3rd, Kim J, O’Brien KD, Chait A. Toll-like receptor 4 deficiency decreases atherosclerosis but does not protect against inflammation in obese low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2012;32(7):1596–1604.
  • Cosgrove HA, Gingras S, Kim M, Bastacky S, Tilstra JS, Shlomchik MJ. B cell-intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice. JCI Insight. 2023;8(16):e172219.
  • Hennessy EJ, Parker AE, O’Neill LA. Targeting Toll-like receptors: emerging therapeutics? Nat Rev Drug Discov. 2010;9(4):293–307.
  • Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, Wittebole X, Dugernier T, Perrotin D, Tidswell M, et al. Effect of eritoran, an antagonist of MD2-TLR4, on mortality in patients with severe sepsis: the ACCESS randomized trial. JAMA. 2013;309(11):1154–1162.
  • Rice TW, Wheeler AP, Bernard GR, Vincent JL, Angus DC, Aikawa N, Demeyer I, Sainati S, Amlot N, Cao C, et al. A randomized, double-blind, placebo-controlled trial of TAK-242 for the treatment of severe sepsis. Crit Care Med. 2010;38(8):1685–1694.
  • Ngo HX, Garneau-Tsodikova S. What are the drugs of the future? MedChemComm. 2018;9(5):757–758.
  • Valkov E, Stamp A, Dimaio F, Baker D, Verstak B, Roversi P, Kellie S, Sweet MJ, Mansell A, Gay NJ, et al. Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection. Proc Natl Acad Sci U S A. 2011;108(36):14879–14884.
  • Lin Z, Lu J, Zhou W, Shen Y. Structural insights into TIR domain specificity of the bridging adaptor Mal in TLR4 signaling. PLOS One. 2012;7(4):e34202–e34202.
  • Snyder GA, Deredge D, Waldhuber A, Fresquez T, Wilkins DZ, Smith PT, Durr S, Cirl C, Jiang J, Jennings W, et al. Crystal structures of the Toll/interleukin-1 receptor (TIR) domains from the Brucella protein TcpB and host adaptor TIRAP reveal mechanisms of molecular mimicry. J Biol Chem. 2014;289(2):669–679.
  • Woo JR, Kim S, Shoelson SE, Park S. X-ray crystallographic structure of TIR-domain from the human TIR-domain containing adaptor protein/MyD88-adaptor-like protein (TIRAP/MAL). B Korean Chem Soc. 2012;33(9):3091–3094.
  • Hughes MM, Lavrencic P, Coll RC, Ve T, Ryan DG, Williams NC, Menon D, Mansell A, Board PG, Mobli M, et al. Solution structure of the TLR adaptor MAL/TIRAP reveals an intact BB loop and supports MAL Cys91 glutathionylation for signaling. Proc Natl Acad Sci U S A. 2017;114(32):E6480–E6489.
  • Ve T, Vajjhala PR, Hedger A, Croll T, DiMaio F, Horsefield S, Yu X, Lavrencic P, Hassan Z, Morgan GP, et al. Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. Nat Struct Mol Biol. 2017;24(9):743–751.
  • Vajjhala PR, Ve T, Bentham A, Stacey KJ, Kobe B. The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways. Mol Immunol. 2017;86:23–37.
  • Clabbers MTB, Holmes S, Muusse TW, Vajjhala PR, Thygesen SJ, Malde AK, Hunter DJB, Croll TI, Flueckiger L, Nanson JD, et al. MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography. Nat Commun. 2021;12(1):2578.
  • Dowling JK, Tate MD, Rosli S, Bourke NM, Bitto N, Lauterbach MA, Cheung S, Ve T, Kobe B, Golenbock D, et al. The single nucleotide polymorphism Mal-D96N mice provide new insights into functionality of Mal in TLR immune responses. J Immunol. 2019;202(8):2384–2396.
  • Piao W, Shirey KA, Ru LW, Lai W, Szmacinski H, Snyder GA, Sundberg EJ, Lakowicz JR, Vogel SN, Toshchakov VY. A decoy peptide that disrupts TIRAP recruitment to TLRs is protective in a murine model of influenza. Cell Rep. 2015;11(12):1941–1952.
  • Mistry P, Laird MH, Schwarz RS, Greene S, Dyson T, Snyder GA, Xiao TS, Chauhan J, Fletcher S, Toshchakov VY, et al. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain. Proc Natl Acad Sci U S A. 2015;112(17):5455–5460.
  • Stacey KJ, Young GR, Clark F, Sester DP, Roberts TL, Naik S, Sweet MJ, Hume DA. The molecular basis for the lack of immunostimulatory activity of vertebrate DNA. J Immunol. 2003;170(7):3614–3620.
  • Hill JM. NMR screening for rapid protein characterization in structural proteomics. Methods Mol Biol. 2008;426:437–446.
  • Mobli M, Maciejewski MW, Gryk MR, Hoch JC. An automated tool for maximum entropy reconstruction of biomolecular NMR spectra. Nat Methods. 2007;4(6):467–468.
  • Vranken WF, Boucher W, Stevens TJ, Fogh RH, Pajon A, Llinas M, Ulrich EL, Markley JL, Ionides J, Laue ED. The CCPN data model for NMR spectroscopy: development of a software pipeline. Proteins. 2005;59(4):687–696.
  • Güntert P, Mumenthaler C, Wüthrich K. Torsion angle dynamics for NMR structure calculation with the new program DYANA. J Mol Biol. 1997;273(1):283–298.
  • Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE. UCSF Chimera–a visualization system for exploratory research and analysis. J Comput Chem. 2004;25(13):1605–1612.
  • Sester DP, Thygesen SJ, Sagulenko V, Vajjhala PR, Cridland JA, Vitak N, Chen KW, Osborne GW, Schroder K, Stacey KJ. A novel flow cytometric method to assess inflammasome formation. J Immunol. 2015;194(1):455–462.
  • Muusse TW, Lee MYL, Kim H, Parat MO, Nanson JD, Kobe B, Vajjhala PR, Stacey KJ. Flow cytometric reporter assays provide robust functional analysis of signaling complexes. J Biol Chem. 2022;298(12):102666.
  • Miljenović T, Jia X, Lavrencic P, Kobe B, Mobli M. A non-uniform sampling approach enables studies of dilute and unstable proteins. J Biomol Nmr. 2017;68(2):119–127.
  • Ve T, Williams SJ, Kobe B. Structure and function of Toll/interleukin-1 receptor/resistance protein (TIR) domains. Apoptosis. 2015;20(2):250–261.
  • Sharma D, Rajarathnam K. 13C NMR chemical shifts can predict disulfide bond formation. J Biomol Nmr. 2000;18(2):165–171.
  • Dal Corso A, Catalano M, Schmid A, Scheuermann J, Neri D. Affinity enhancement of protein ligands by reversible covalent modification of neighboring lysine residues. Angew Chem Int Ed Engl. 2018;57(52):17178–17182.
  • Zaugg RH, Walder JA, Klotz IM. Schiff base adducts of hemoglobin. Modifications that inhibit erythrocyte sickling. J Biol Chem. 1977;252(23):8542–8548.
  • Sharp TR, Morris R, Horan GJ, Pezzullo LH, Stroh JG. Method for determining the average degree of substitution of o-vanillin derivatized porcine somatotropin. J Pharm Biomed Anal. 2006;40(1):185–189.
  • Farrar MR, Lakshmi KV, Smith SO, Brown RS, Raap J, Lugtenburg J, Griffin RG, Herzfeld J. Solid state NMR study of [epsilon-13C]Lys-bacteriorhodopsin: schiff base photoisomerization. Biophys J. 1993;65(1):310–315.
  • Sato K, Taniguchi T, Suzuki M, Shinohara F, Takada H, Rikiishi H. Dual role of NF-kappaB in apoptosis of THP-1 cells during treatment with etoposide and lipopolysaccharide. Leuk Res. 2004;28(1):63–69.
  • Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T, Hoshino K, Takeuchi O, Kobayashi M, Fujita T, et al. Essential role for TIRAP in activation of the signalling cascade shared by TLR2 and TLR4. Nature. 2002;420(6913):324–329.
  • Horng T, Barton GM, Flavell RA, Medzhitov R. The adaptor molecule TIRAP provides signalling specificity for Toll-like ­receptors. Nature. 2002;420(6913):329–333.
  • Cole LE, Laird MH, Seekatz A, Santiago A, Jiang Z, Barry E, Shirey KA, Fitzgerald KA, Vogel SN. Phagosomal retention of Francisella tularensis results in TIRAP/Mal-independent TLR2 signaling. J Leukoc Biol. 2010;87(2):275–281.
  • Kenny EF, Talbot S, Gong M, Golenbock DT, Bryant CE, O’Neill LA. MyD88 adaptor-like is not essential for TLR2 signaling and inhibits signaling by TLR3. J Immunol. 2009;183(6):3642–3651.
  • Alam S, Javor S, Degardin M, Ajami D, Rebek M, Kissner TL, Waag DM, Rebek J, Saikh KU. Structure-based design and synthesis of a small molecule that exhibits anti-inflammatory activity by inhibition of MyD88-mediated signaling to bacterial toxin exposure. Chem Biol Drug Des. 2015;86(2):200–209.
  • Loiarro M, Capolunghi F, Fantò N, Gallo G, Campo S, Arseni B, Carsetti R, Carminati P, De Santis R, Ruggiero V, et al. Pivotal advance: inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound. J Leukoc Biol. 2007;82(4):801–810.
  • Capolunghi F, Rosado MM, Cascioli S, Girolami E, Bordasco S, Vivarelli M, Ruggiero B, Cortis E, Insalaco A, Fantò N, et al. Pharmacological inhibition of TLR9 activation blocks autoantibody production in human B cells from SLE patients. Rheumatology. 2010;49(12):2281–2289.
  • Zhang HS, Li H, Zhang DD, Yan HY, Zhang ZH, Zhou CH, Ye ZN, Chen Q, Jiang TW, Liu JP, et al. Inhibition of myeloid differentiation factor 88(MyD88) by ST2825 provides neuroprotection after experimental traumatic brain injury in mice. Brain Res. 2016;1643:130–139.
  • Wang X, Tan Y, Huang Z, Huang N, Gao M, Zhou F, Hu J, Feng W. Disrupting myddosome assembly in diffuse large B-cell lymphoma cells using the MYD88 dimerization inhibitor ST2825. Oncol Rep. 2019;42(5):1755–1766.
  • Ippagunta SK, Pollock JA, Sharma N, Lin W, Chen T, Tawaratsumida K, High AA, Min J, Chen Y, Guy RK, et al. Identification of Toll-like receptor signaling inhibitors based on selective activation of hierarchically acting signaling proteins. Sci Signal. 2018;11(543):eaaq1077.
  • Toshchakov VY, Javmen A. Targeting the TLR signalosome with TIR domain-derived cell-permeable decoy peptides: the current state and perspectives. Innate Immun. 2020;26(1):35–47.
  • Shuker SB, Hajduk PJ, Meadows RP, Fesik SW. Discovering high-affinity ligands for proteins: SAR by NMR. Science. 1996;274(5292):1531–1534.
  • Azar DF, Haas M, Fedosyuk S, Rahaman MH, Hedger A, Kobe B, Skern T. Vaccinia virus immunomodulator A46: destructive interactions with MAL and MyD88 shown by negative-stain electron microscopy. Structure. 2020;28(12):1271–1287 e5.
  • Spear AM, Rana RR, Jenner DC, Flick-Smith HC, Oyston PCF, Simpson P, Matthews SJ, Byrne B, Atkins HS. A Toll/interleukin (IL)-1 receptor domain protein from Yersinia pestis interacts with mammalian IL-1/Toll-like receptor pathways but does not play a central role in the virulence of Y. pestis in a mouse model of bubonic plague. Microbiology (Reading). 2012;158(Pt 6):1593–1606.
  • Hacker SM, Backus KM, Lazear MR, Forli S, Correia BE, Cravatt BF. Global profiling of lysine reactivity and ligandability in the human proteome. Nat Chem. 2017;9(12):1181–1190.