Crystal structure of the Toll/interleukin-1 receptor (TIR) domain of IL-1R10 provides structural insights into TIR domain signalling Surekha Nimma, Weixi Gu, Mohammad K. Manik, Thomas Ve, Jeffrey D. Nanson, et al. FEBS Letters, 2022 The Toll/interleukin-1 receptor (TIR) domains are key innate immune signaling modules. Here, we present the crystal structure of the TIR domain of human Interleukin-1 receptor 10 (IL-1R10), also called IL-1RAPL2. It is similar to that of IL-1R9 (IL-1RAPL1) but shows significant structural differences to those from Toll-like receptors (TLRs) and the adaptor proteins MAL and MyD88. Interactions of TIR domains in their respective crystals and the higher-order assemblies (MAL and MyD88) reveal the presence of a common 'BCD surface', suggesting its functional significance. We also show that the TIR domains of IL-1R10 and IL-1R9 lack NADase activity, consistent with their structures. Our study provides a foundation for unraveling the functions of IL-1R9 and IL-1R10.
Structural Evolution of TIR-Domain Signalosomes Surekha Nimma, Weixi Gu, Natsumi Maruta, Yan Li, Mengqi Pan, et al. Frontiers in Immunology, 2021 TIR (Toll/interleukin-1 receptor/resistance protein) domains are cytoplasmic domains widely found in animals and plants, where they are essential components of the innate immune system. A key feature of TIR-domain function in signaling is weak and transient self-association and association with other TIR domains. An additional new role of TIR domains as catalytic enzymes has been established with the recent discovery of NAD+-nucleosidase activity by several TIR domains, mostly involved in cell-death pathways. Although self-association of TIR domains is necessary in both cases, the functional specificity of TIR domains is related in part to the nature of the TIR : TIR interactions in the respective signalosomes. Here, we review the well-studied TIR domain-containing proteins involved in eukaryotic immunity, focusing on the structures, interactions and their corresponding functional roles. Structurally, the signalosomes fall into two separate groups, the scaffold and enzyme TIR-domain assemblies, both of which feature open-ended complexes with two strands of TIR domains, but differ in the orientation of the two strands. We compare and contrast how TIR domains assemble and signal through distinct scaffolding and enzymatic roles, ultimately leading to distinct cellular innate-immunity and cell-death outcomes.
Towards the structure of the TIR-domain signalosome Surekha Nimma, Thomas Ve, Simon J. Williams, Bostjan Kobe Current Opinion in Structural Biology, 2017 TIR (Toll/interleukin-1 receptor/resistance protein) domains feature in animal, plant and bacterial proteins involved in innate immunity pathways and associated processes. They function through protein:protein interactions, in particular self-association and homotypic association with other TIR domains. Structures of TIR domains from all phyla have been determined, but common association modes have only emerged for plant and bacterial TIR domains, and not for mammalian TIR domains. Numerous attempts involving hybrid approaches, which have combined structural, computational, mutagenesis and biophysical data, have failed to converge onto common models of how these domains associate and function. We propose that the available data can be reconciled in the context of higher-order assembly formation, and that TIR domains function through signaling by cooperative assembly formation (SCAF).
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Structural and functional characterization of Interleukin-1 receptor 8 A Alenzi, S Nimma, B Kobe Acta Cryst 79, C955 , 2023 2023
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Crystal structure of the Toll/interleukin‐1 receptor (TIR) domain of IL‐1R10 provides structural insights into TIR domain signalling S Nimma, W Gu, MK Manik, T Ve, JD Nanson, B Kobe FEBS letters 596 (7), 886-897 , 2022 2022 Citations: 13
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Structural evolution of TIR-domain signalosomes S Nimma, W Gu, N Maruta, Y Li, M Pan, FK Saikot, BYJ Lim, ... Frontiers in immunology 12, 784484 , 2021 2021 Citations: 67
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MOST CITED SCHOLAR PUBLICATIONS
Towards the structure of the TIR-domain signalosome S Nimma, T Ve, SJ Williams, B Kobe Current opinion in structural biology 43, 122-130 , 2017 2017 Citations: 85
Structural evolution of TIR-domain signalosomes S Nimma, W Gu, N Maruta, Y Li, M Pan, FK Saikot, BYJ Lim, ... Frontiers in immunology 12, 784484 , 2021 2021 Citations: 67
Design of new hybrid template by linking quinoline, triazole and dihydroquinoline pharmacophoric groups: A greener approach to novel polyazaheterocycles as cytotoxic agents KSS Praveena, EVVS Ramarao, NYS Murthy, S Akkenapally, CG Kumar, ... Bioorganic & Medicinal Chemistry Letters 25 (5), 1057-1063 , 2015 2015 Citations: 54
Synthesis of 2, 2, 4-trimethyl-1, 2-dihydroquinolinyl substituted 1, 2, 3-triazole derivatives: Their evaluation as potential PDE 4B inhibitors possessing cytotoxic properties … KSS Praveena, S Durgadas, NS Babu, S Akkenapally, CG Kumar, ... Bioorganic Chemistry 53, 8-14 , 2014 2014 Citations: 39
Evaluation of critical nutritional parameters and their significance in the production of rhamnolipid biosurfactants from Pseudomonas aeruginosa BS‐161R CG Kumar, SK Mamidyala, P Sujitha, H Muluka, S Akkenapally Biotechnology progress 28 (6), 1507-1516 , 2012 2012 Citations: 38
Crystal structure of the Toll/interleukin‐1 receptor (TIR) domain of IL‐1R10 provides structural insights into TIR domain signalling S Nimma, W Gu, MK Manik, T Ve, JD Nanson, B Kobe FEBS letters 596 (7), 886-897 , 2022 2022 Citations: 13
Production of recombinant coiled coil silk proteins for materials synthesis PJ Shilling, L Pontes-Braz, L Mitchell, L Howell, P Veneer, S Jayashree, ... Protein Expression and Purification 229, 106683 , 2025 2025 Citations: 2
Structural and functional characterization of Interleukin-1 receptor 8 A Alenzi, S Nimma, B Kobe Acta Cryst 79, C955 , 2023 2023
Determining the role of TIR domains of interleukin-1 receptors in TLR/IL-1R signalling S Nimma 2023
Crystal structure of the TIR domain of IL-1R10 provides structural 2 insights into TIR domain signaling S Nimma, W Gu, MK Manik, T Ve, JD Nanson, B Kobe 2022
Determining the role of TIR domain of Interleukin-1 receptor 8 (SIGIRR) in regulating TLR4 signalling S Nimma, J Nanson, T Ve, B Kobe Acta Cryst 77, C785 , 2021 2021
