MyD88 TIR domain higher-order assembly interactions revealed by microcrystal electron diffraction and serial femtosecond crystallography.

Autor: Clabbers MTB; Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden.; Department of Biological Chemistry, University of California Los Angeles, Los Angeles, California, USA., Holmes S; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia., Muusse TW; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Vajjhala PR; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Thygesen SJ; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Malde AK; Institute for Glycomics, Griffith University, Southport, Queensland, Australia., Hunter DJB; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.; EMBL Australia Node in Single Molecule Science, University of New South Wales, Kensington, New South Wales, Australia.; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia., Croll TI; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK., Flueckiger L; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia., Nanson JD; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Rahaman MH; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia., Aquila A; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA., Hunter MS; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA., Liang M; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA., Yoon CH; Linac Coherent Light Source, SLAC National Accelerator Laboratory, Menlo Park, California, USA., Zhao J; Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden., Zatsepin NA; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia., Abbey B; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia., Sierecki E; EMBL Australia Node in Single Molecule Science, University of New South Wales, Kensington, New South Wales, Australia., Gambin Y; EMBL Australia Node in Single Molecule Science, University of New South Wales, Kensington, New South Wales, Australia., Stacey KJ; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia., Darmanin C; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia. c.darmanin@latrobe.edu.au., Kobe B; School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia. b.kobe@uq.edu.au.; Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia. b.kobe@uq.edu.au.; Australian Infectious Diseases Research Centre, The University of Queensland, Brisbane, Queensland, Australia. b.kobe@uq.edu.au., Xu H; Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden. hongyi.xu@mmk.su.se., Ve T; Institute for Glycomics, Griffith University, Southport, Queensland, Australia. t.ve@griffith.edu.au.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 May 10; Vol. 12 (1), pp. 2578. Date of Electronic Publication: 2021 May 10.
DOI: 10.1038/s41467-021-22590-6
Abstrakt: MyD88 and MAL are Toll-like receptor (TLR) adaptors that signal to induce pro-inflammatory cytokine production. We previously observed that the TIR domain of MAL (MAL TIR ) forms filaments in vitro and induces formation of crystalline higher-order assemblies of the MyD88 TIR domain (MyD88 TIR ). These crystals are too small for conventional X-ray crystallography, but are ideally suited to structure determination by microcrystal electron diffraction (MicroED) and serial femtosecond crystallography (SFX). Here, we present MicroED and SFX structures of the MyD88 TIR assembly, which reveal a two-stranded higher-order assembly arrangement of TIR domains analogous to that seen previously for MAL TIR . We demonstrate via mutagenesis that the MyD88 TIR assembly interfaces are critical for TLR4 signaling in vivo, and we show that MAL promotes unidirectional assembly of MyD88 TIR . Collectively, our studies provide structural and mechanistic insight into TLR signal transduction and allow a direct comparison of the MicroED and SFX techniques.
Databáze: MEDLINE
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