The present work analyzed the tetrameric stability of the hemoglobins from the rattlesnake C. durissus terrificus using analytical gel filtration chromatography, SAXS and osmotic stress. We show that the dissociation mechanism proposed for L. miliaris hemoglobin does not apply for these hemoglobins, which constitute stable tetramers even at low concentrations.
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http://dx.doi.org/10.2174/092986606776819484 | DOI Listing |
Protein Sci
February 2025
Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, Alberta, Canada.
Polymyxins are last-resort antimicrobial peptides administered clinically against multi-drug resistant bacteria, specifically in the case of Gram-negative species. However, an increasing number of these pathogens employ a defense strategy that involves a relay of enzymes encoded by the pmrE (ugd) loci and the arnBCDTEF operon. The pathway modifies the lipid-A component of the outer membrane (OM) lipopolysaccharide (LPS) by adding a 4-amino-4-deoxy-l-arabinose (L-Ara4N) headgroup, which renders polymyxins ineffective.
View Article and Find Full Text PDFNat Struct Mol Biol
January 2025
Department of Integrative Structural and Computational Biology, Scripps Research, La Jolla, CA, USA.
Transthyretin (TTR) is a natively tetrameric thyroxine transporter in blood and cerebrospinal fluid whose misfolding and aggregation causes TTR amyloidosis. A rational drug design campaign identified the small molecule tafamidis (Vyndamax) as a stabilizer of the native TTR fold, and this aggregation inhibitor is regulatory agency approved for the treatment of TTR amyloidosis. Here we used cryo-EM to investigate the conformational landscape of this 55 kDa tetramer in the absence and presence of one or two ligands, revealing inherent asymmetries in the tetrameric architecture and previously unobserved conformational states.
View Article and Find Full Text PDFProteins
January 2025
Institute of Molecular Biosciences, University of Graz, Graz, Austria.
The Old Yellow Enzyme from Ferrovum sp. JA12 (FOYE) displays an unusual thermal stability for an enzyme isolated from a mesophilic organism. We determined the crystal structure of this enzyme and performed bioinformatic characterization to get insights into its thermal stability.
View Article and Find Full Text PDFFront Pharmacol
January 2025
IDiBE-Instituto de Investigación, Desarrollo e Innovación en Biotecnología Sanitaria de Elche, Universidad Miguel Hernández, Elche, Spain.
The Selectivity Filter (SF) in tetrameric K channels, has a highly conserved sequence, TVGYG, at the extracellular entry to the channel pore region. There, the backbone carbonyl oxygens from the SF residues, create a stack of K binding sites where dehydrated K binds to induce a conductive conformation of the SF. This increases intersubunit interactions and confers a higher stability to the channel against thermal denaturation.
View Article and Find Full Text PDFMatrix Biol
January 2025
Manchester Cell-Matrix Centre, Division of Cell-Matrix Biology and Regenerative Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK; Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, M13 9PL, United Kingdom. Electronic address:
Pentraxin-3 (PTX3) is an octameric protein, comprised of eight identical protomers, that has diverse functions in reproductive biology, innate immunity and cancer. PTX3 interacts with the large polysaccharide hyaluronan (HA) to which heavy chains (HCs) of the inter-α-inhibitor (IαI) family of proteoglycans are covalently attached, playing a key role in the (non-covalent) crosslinking of HC•HA complexes. These interactions stabilise the cumulus matrix, essential for ovulation and fertilisation in mammals, and are also implicated in the formation of pathogenic matrices in the context of viral lung infections.
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