Mass Spectrometry-based Structural Analysis and Systems Immunoproteomics Strategies for Deciphering the Host Response to Endotoxin. Issue 17 (17th August 2018)

• Record Type: Journal Article
• Authors: Khan, Mohd M.; Ernst, Orna; Sun, Jing; Fraser, Iain D.C.; Ernst, Robert K.; Goodlett, David R.; Nita-Lazar, Aleksandra
• Is Part Of: Journal of molecular biology. Volume 430:Issue 17(2018)
• Page Start: 2641
• Page End: 2660
• Publication Date: 2018-08-17
• Subjects: ADAM10 a disintegrin and metalloproteinase domain-containing protein 10 -- MMP14 matrix metalloproteinase-14 -- HSP heat shock protein -- BECC bacterial enzymatic combinatorial chemistry -- DAMPs danger-associated molecular patterns -- LPS lipopolysaccharide -- TLR4 Toll-like receptor 4 -- MS mass spectrometry -- RNAi RNA interference -- OMVs outer-membrane vesicles -- R-LPS rough LPS -- GlcN glucosamine -- GlcNAc N-acetylglucosamine -- mTOR mammalian target of rapamycin -- MPLA monophosphoryl lipid A -- P3C Pam3CysSK4 -- R848 resiquimod -- MD2 myeloid differentiation factor-2 -- MS mass spectrometry -- PTMs post-translational modifications -- HMGB-1 high mobility group box-1 -- LBP lipopolysaccharide-binding protein -- MyD88 myeloid differentiation primary response gene 88 -- TRIF TIR domain-containing adapter-inducing interferon-β -- TRAM TRIF-related adaptor molecule -- IFN interferon regulatory factors -- MAPK mitogen-activated protein kinases -- ERK extracellular signal-regulated kinase -- MEK extracellular signal-regulated kinase -- NF-κB nuclear transcription factor κB -- TNF-α tumor necrosis factor α -- ASC apoptosis-associated speck-like protein containing a carboxy-terminal CARD -- NLRP3 NOD-like receptor pyrin-domain containing 3 -- CARD C-terminal CARD protein–protein interaction domain -- SAR structure–activity relationship -- CD14 cluster of differentiation 14 -- CXCR4 C-X-C chemokine receptor type 4 -- GDF5 growth differentiation factor 5 -- GNB Gram-negative bacteria -- Aim 2 absent in melanoma 2 -- NEK7 NIMA-related kinase 7 -- Akt also known as protein kinase B -- TPL-2 tumor progression locus 2 (TPL-2 aka MAP3K8) kinase -- FPI effectors encoded by the Francisella pathogenicity island -- PICALM phosphatidylinositol binding clathrin assembly protein -- AP1AR AP-1 complex-associated regulatory protein -- IKK IκB kinase -- TRAF TNF receptor-associated factor -- TANK TRAF family member-associated NFκB activator -- TBK1 TANK-binding kinase 1 -- UBC13 E2 ubiquitin ligase UBC13 -- HOIP E3 ubiquitin ligase HOIP -- IRAK Interleukin-1 receptor-associated kinase -- MaI myelin and lymphocyte protein -- NEU-1 neuraminidase-1 -- SUMO small ubiquitin-like modifier -- RIG retinoic acid-inducible gene -- NOD nucleotide-binding oligomerization domain -- RNAi RNA interference -- PAMPs pathogen-associated molecular patterns -- PRRs pattern recognition receptors -- IRF3 interferon regulatory factor 3 -- MALP-2 mycoplasmal macrophage-activating lipopeptide-2 kD -- FADD FAS-associated death domain protein -- RIPK1 receptor-interacting serine/threonine-protein kinase 1 -- TNFR1 tumor necrosis factor receptor 1 -- TRADD TNFR1-associated death domain protein; Proteomics -- LPS -- TLR4 -- caspase-4/5/11 -- innate and adaptive immunity; Molecular biology -- Periodicals; Biology -- Periodicals; Biochemistry -- Periodicals; Bacteriology -- Periodicals; Molecular Biology -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biologie -- Périodiques; Biochimie -- Périodiques; Moleculaire biologie; Biochemistry; Biology; Molecular biology; Periodicals; 572.805
• DOI: 10.1016/j.jmb.2018.06.032
• Languages: English
• ISSNs: 0022-2836

Abstract

Abstract: One cause of sepsis is systemic maladaptive immune response of the host to bacteria and specifically, to Gram-negative bacterial outer-membrane glycolipid lipopolysaccharide (LPS). On the host myeloid cell surface, proinflammatory LPS activates the innate immune system via Toll-like receptor-4/myeloid differentiation factor-2 complex. Intracellularly, LPS is also sensed by the noncanonical inflammasome through caspase-11 in mice and 4/5 in humans. The minimal functional determinant for innate immune activation is the membrane anchor of LPS called lipid A. Even subtle modifications to the lipid A scaffold can enable, diminish, or abolish immune activation. Bacteria are known to modify their LPS structure during environmental stress and infection of hosts to alter cellular immune phenotypes. In this review, we describe how mass spectrometry-based structural analysis of endotoxin helped uncover major determinations of molecular pathogenesis. Through characterization of LPS modifications, we now better understand resistance to antibiotics and cationic antimicrobial peptides, as well as how the environment impacts overall endotoxin structure. In addition, mass spectrometry-based systems immunoproteomics approaches can assist in elucidating the immune response against LPS. Many regulatory proteins have been characterized through proteomics and global/targeted analysis of protein modifications, enabling the discovery and characterization of novel endotoxin-mediated protein translational modifications. Graphical abstract: Unlabelled Image Highlights: The structure of Gram-negative bacterial outer-membrane component, lipopolysaccharide (LPS), affects the host immune response; bacteria produce diverse LPS scaffolds that have a wide range of immune potentials. Extracellular LPS is recognized by the host's Toll-like receptor 4/myeloid differentiation factor-2 complex; intracellular recognition of LPS is mediated by the host non-canonical inflammasome machinery (through caspase-4/5/11). MS-based LPS analyses have contributed to our understanding of how bacteria remodel their lipid A, the functional determinant of endotoxins' recognition by the host innate immune system. Mass spectrometry-based system immunoproteomics is a key technology applied to evaluate host–pathogen interactions such as through the analysis of proteome, secretome, and post-translational modifications (e.g., the phosphoproteome). Recent contributions in clinical proteomics have helped determine the etiology of septic shock. These studies pave a way forward for future multi-omics-based immune system investigations.