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Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides.

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Saravanan R, Holdbrook DA, Petrlova J, Singh S, Berglund NA, Choong YK, Kjellström S, Bond PJ, Malmsten M, Schmidtchen A
OpenAccess logo Nat Commun 9 2762 (2018)
Cited: 25 times
EuropePMC logo PMID: 30018388

Abstract

Thrombin-derived C-terminal peptides (TCPs) of about 2 kDa are present in wounds, where they exert anti-endotoxic functions. Employing a combination of nuclear magnetic resonance spectroscopy (NMR), biophysical, mass spectrometry and cellular studies combined with in silico multiscale modelling, we here determine the bound conformation of HVF18 (HVFRLKKWIQKVIDQFGE), a TCP generated by neutrophil elastase, in complex with bacterial lipopolysaccharide (LPS) and define a previously undisclosed interaction between TCPs and human CD14. Further, we show that TCPs bind to the LPS-binding hydrophobic pocket of CD14 and identify the peptide region crucial for TCP interaction with LPS and CD14. Taken together, our results demonstrate the role of structural transitions in LPS complex formation and CD14 interaction, providing a molecular explanation for the previously observed therapeutic effects of TCPs in experimental models of bacterial sepsis and endotoxin shock.

Articles - 5z5w mentioned but not cited (1)

  1. Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides. Saravanan R, Holdbrook DA, Petrlova J, Singh S, Berglund NA, Choong YK, Kjellström S, Bond PJ, Malmsten M, Schmidtchen A. Nat Commun 9 2762 (2018)


Reviews citing this publication (5)

  1. Design, Engineering and Discovery of Novel α-Helical and β-Boomerang Antimicrobial Peptides against Drug Resistant Bacteria. Bhattacharjya S, Straus SK. Int J Mol Sci 21 E5773 (2020)
  2. Thanatin: An Emerging Host Defense Antimicrobial Peptide with Multiple Modes of Action. Dash R, Bhattacharjya S. Int J Mol Sci 22 1522 (2021)
  3. Synergy by Perturbing the Gram-Negative Outer Membrane: Opening the Door for Gram-Positive Specific Antibiotics. Wesseling CMJ, Martin NI. ACS Infect Dis 8 1731-1757 (2022)
  4. Atomic-Resolution Structures and Mode of Action of Clinically Relevant Antimicrobial Peptides. Bhattacharjya S, Mohid SA, Bhunia A. Int J Mol Sci 23 4558 (2022)
  5. Mammals' humoral immune proteins and peptides targeting the bacterial envelope: from natural protection to therapeutic applications against multidrug-resistant Gram-negatives. Escobar-Salom M, Torrens G, Jordana-Lluch E, Oliver A, Juan C. Biol Rev Camb Philos Soc 97 1005-1037 (2022)

Articles citing this publication (19)

  1. SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity. Petruk G, Puthia M, Petrlova J, Samsudin F, Strömdahl AC, Cerps S, Uller L, Kjellström S, Bond PJ, Schmidtchen AA. J Mol Cell Biol 12 916-932 (2020)
  2. High-Throughput Identification of Putative Antimicrobial Peptides from Multi-Omics Data of the Lined Seahorse (Hippocampus erectus). Chen X, Yi Y, You X, Liu J, Shi Q. Mar Drugs 18 E30 (2019)
  3. Reactive metal boride nanoparticles trap lipopolysaccharide and peptidoglycan for bacteria-infected wound healing. Meng Y, Chen L, Chen Y, Shi J, Zhang Z, Wang Y, Wu F, Jiang X, Yang W, Zhang L, Wang C, Meng X, Wu Y, Bu W. Nat Commun 13 7353 (2022)
  4. Experimental Model of Pulmonary Inflammation Induced by SARS-CoV-2 Spike Protein and Endotoxin. Puthia M, Tanner L, Petruk G, Schmidtchen A. ACS Pharmacol Transl Sci 5 141-148 (2022)
  5. Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Pediatric Sepsis. Xie K, Kong S, Li F, Zhang Y, Wang J, Zhao W. Med Sci Monit 26 e923881 (2020)
  6. SARS-CoV-2 spike protein aggregation is triggered by bacterial lipopolysaccharide. Petrlova J, Samsudin F, Bond PJ, Schmidtchen A. FEBS Lett 596 2566-2575 (2022)
  7. Cell-Free DNA Promotes Thrombin Autolysis and Generation of Thrombin-Derived C-Terminal Fragments. Saravanan R, Choong YK, Lim CH, Lim LM, Petrlova J, Schmidtchen A. Front Immunol 12 593020 (2021)
  8. Direct Measurement of Through-Bond Effects in Molecular Multivalent Interactions. Feng X, Yu C, Feng F, Lu P, Chai Y, Li Q, Zhang D, Wang X, Yao L. Chemistry 25 2978-2982 (2019)
  9. Highly Sensitive Endotoxin Assay Combining Peptide/Graphene Oxide and DNA-Modified Gold Nanoparticles. Yu N, Zhang X, Gao Y, You H, Zhang J, Miao P. ACS Omega 4 14312-14316 (2019)
  10. Thrombin-Derived Peptides Potentiate the Activity of Gram-Positive-Specific Antibiotics against Gram-Negative Bacteria. Wesseling CMJ, Wood TM, Bertheussen K, Lok S, Martin NI. Molecules 26 1954 (2021)
  11. Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25. Petruk G, Petrlova J, Samsudin F, Giudice RD, Bond PJ, Schmidtchen A. Biomolecules 10 E1572 (2020)
  12. In Situ Neutralization and Detoxification of LPS to Attenuate Hyperinflammation. Li X, Qu S, Song X, Wu C, Shen J, Zhu K. Adv Sci (Weinh) 10 e2302950 (2023)
  13. Differential Internalization of Thrombin-Derived Host Defense Peptides into Monocytes and Macrophages. Hansen FC, Nadeem A, Browning KL, Campana M, Schmidtchen A, van der Plas MJA. J Innate Immun 14 418-432 (2022)
  14. Environment-Sensitive Fluorescent Labelling of Peptides by Luciferin Analogues. Siepi M, Oliva R, Masino A, Gaglione R, Arciello A, Russo R, Di Maro A, Zanfardino A, Varcamonti M, Petraccone L, Del Vecchio P, Merola M, Pizzo E, Notomista E, Cafaro V. Int J Mol Sci 22 13312 (2021)
  15. Interaction of Pexiganan (MSI-78)-Derived Analogues Reduces Inflammation and TLR4-Mediated Cytokine Secretion: A Comparative Study. Cohen H, Wani NA, Ben Hur D, Migliolo L, Cardoso MH, Porat Z, Shimoni E, Franco OL, Shai Y. ACS Omega 8 17856-17868 (2023)
  16. Thrombin-Derived C-Terminal Peptide Reduces Candida-Induced Inflammation and Infection In Vitro and In Vivo. Dahlman A, Puthia M, Petrlova J, Schmidtchen A, Petruk G. Antimicrob Agents Chemother 65 e0103221 (2021)
  17. Rapid in vitro and in vivo Evaluation of Antimicrobial Formulations Using Bioluminescent Pathogenic Bacteria. Schmidtchen A, Puthia M. Bio Protoc 12 e4302 (2022)
  18. Selective protein aggregation confines and inhibits endotoxins in wounds: Linking host defense to amyloid formation. Petrlova J, Hartman E, Petruk G, Lim JCH, Adav SS, Kjellström S, Puthia M, Schmidtchen A. iScience 26 107951 (2023)
  19. Targeting Toll-like receptor-driven systemic inflammation by engineering an innate structural fold into drugs. Petruk G, Puthia M, Samsudin F, Petrlova J, Olm F, Mittendorfer M, Hyllén S, Edström D, Strömdahl AC, Diehl C, Ekström S, Walse B, Kjellström S, Bond PJ, Lindstedt S, Schmidtchen A. Nat Commun 14 6097 (2023)


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