Berglund Nils

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

Published date : 17 Aug 2018

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.

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Journal Paper
journal
Nature Communications, 2018 Jul 17;9(1):2762. doi: 10.1038/s41467-018-05242-0
Impact Factor
12.353

Activation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub

Published date : 26 Jun 2018

Infection and tissue damage induces assembly of supramolecular organizing centres (SMOCs)), such as the Toll-like receptor (TLR) MyDDosome, to co-ordinate inflammatory signaling. SMOC assembly is thought to drive digital all-or-none responses, yet TLR activation by diverse microbes induces anything from mild to severe inflammation. Using single-molecule imaging of TLR4-MyDDosome signaling in living macrophages, we find that MyDDosomes assemble within minutes of TLR4 stimulation.

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Journal Paper
journal
eLife, 2018 Jan 24;7. pii: e31377. doi: 10.7554/eLife.31377
Impact Factor
7.616

Evidence that TLR4 Is Not a Receptor for Saturated Fatty Acids but Mediates Lipid-Induced Inflammation by Reprogramming Macrophage Metabolism

Published date : 19 Apr 2018

Chronic inflammation is a hallmark of obesity and is linked to the development of numerous diseases. The activation of toll-like receptor 4 (TLR4) by long-chain saturated fatty acids (lcSFAs) is an important process in understanding how obesity initiates inflammation. While experimental evidence supports an important role for TLR4 in obesity-induced inflammation in vivo, via a mechanism thought to involve direct binding to and activation of TLR4 by lcSFAs, several lines of evidence argue against lcSFAs being direct TLR4 agonists.

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Journal Paper
journal
Cell Metabolism, Vol. 27, Issue 5, pg 1096-1110, 1 May 2018, doi: 10.1016/j.cmet.2018.03.014
Impact Factor
18.164

The role of protein-protein interactions in Toll-like receptor function

Published date : 02 Jul 2015

As part of the innate immune system, the Toll-like receptors (TLRs) represent key players in the first line of defense against invading foreign pathogens, and are also major targets for therapeutic immunomodulation. TLRs are type I transmembrane proteins composed of an ectodomain responsible for ligand binding, a single-pass transmembrane domain, and a cytoplasmic Toll/Interleukin-1 receptor (TIR) signaling domain.

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Journal Paper
journal
Progress in Biophysics and Molecular Biology, Vol. 119, Issue 1, October 2015, Pages 72–83. doi: 10.1016/j.pbiomolbio.2015.06.021

Interaction of the Antimicrobial Peptide Polymyxin B1 with Both Membranes of E. coli: A Molecular Dynamics Study

Published date : 17 Apr 2015

Antimicrobial peptides are small, cationic proteins that can induce lysis of bacterial cells through interaction with their membranes. Different mechanisms for cell lysis have been proposed, but these models tend to neglect the role of the chemical composition of the membrane, which differs between bacterial species and can be heterogeneous even within a single cell. Moreover, the cell envelope of Gram-negative bacteria such as E. coli contains two membranes with differing compositions.

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Journal Paper
journal
PLOS Computational Biology, doi:10.1371/journal.pcbi.1004180