Bond PJ
Structural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides
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.
ReadSingle mutations in the ε subunit from thermophilic Bacillus PS3 generate a high binding affinity site for ATP
The ε subunit from ATP synthases acts as an ATP sensor in the bacterial cell to prevent ATP hydrolysis and thus the waste of ATP under conditions of low ATP concentration. However, the ATP binding affinities from various bacterial organisms differ markedly, over several orders of magnitude.
ReadThe architecture of the OmpC-MlaA complex sheds light on the maintenance of outer membrane lipid asymmetry in Escherichia coli.
A distinctive feature of the Gram-negative bacterial cell envelope is the asymmetric outer membrane (OM), where lipopolysaccharides and phospholipids (PLs) reside in the outer and inner leaflets, respectively. This unique lipid asymmetry renders the OM impermeable to external insults, including antibiotics and bile salts.
ReadStructural basis for endotoxin neutralisation and anti-inflammatory activity of thrombin-derived C-terminal peptides
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.
ReadActivation of Toll-like receptors nucleates assembly of the MyDDosome signaling hub
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.
ReadA Funneled Conformational Landscape Governs Flavivirus Fusion Peptide Interaction with Lipid Membranes.
During host cell infection by flaviviruses such as dengue and Zika, acidic pH within the endosome triggers a conformational change in the envelope protein on the outer surface of the virion. This results in exposure of the ∼15 residue fusion peptide (FP) region, freeing it to induce fusion between the viral and endosomal membranes.
ReadInfluence of pH on the activity of thrombin-derived antimicrobial peptides
The wound environment is characterized by physiological pH changes. Proteolysis of thrombin by wound-derived proteases, such as neutrophil elastase, generates antimicrobial thrombin-derived C-terminal peptides (TCPs), such as HVF18 (HVFRLKKWIQKVIDQFGE). Presence of such TCPs in human wound fluids in vivo, as well as the occurrence of an evolutionarily conserved His residue in the primary amino acid sequence of TCPs, prompted us to investigate the pH-dependent antibacterial action of HVF18, as well as of the prototypic GKY25 (GKYGFYTHVFRLKKWIQKVIDQFGE).
ReadPartial Intrinsic Disorder Governs the Dengue Capsid Protein Conformational Ensemble
The 11 kDa, positively charged dengue capsid protein (C protein) exists stably as a homodimer and colocalizes with the viral genome within mature viral particles. Its core is composed of four alpha helices encompassing a small hydrophobic patch that may interact with lipids, but approximately 20% of the protein at the N-terminus is intrinsically disordered, making it challenging to elucidate its conformational landscape.
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