title: Supramolecular structure of enterobacterial wild-type lipopolysaccharides (LPS), fractions thereof, and their neutralization by Pep19-2.5.
abstract: Lipopolysaccharides (LPS) belong to the strongest immune-modulating compounds known in nature, and are often described as pathogen-associated molecular patterns (PAMPs). In particular, at higher concentrations they are responsible for sepsis and the septic shock syndrome associated with high lethality. Since most data are indicative that LPS aggregates are the bioactive units, their supramolecular structures are considered to be of outmost relevance for deciphering the molecular mechanisms of its bioactivity. So far, however, most of the data available addressing this issue, were published only for the lipid part (lipid A) and the core-oligosaccharide containing rough LPS, representing the bioactive unit. By contrast, it is well known that most of the LPS specimen identified in natural habitats contain the smooth-form (S-form) LPS, which carry additionally a high-molecular polysaccharide (O-chain). To fill this lacuna and going into a more natural system, here various wild-type (smooth form) LPS including also some LPS fractions were investigated by small-angle X-ray scattering with synchrotron radiation to analyze their aggregate structure. Furthermore, the influence of a recently designed synthetic anti-LPS peptide (SALP) Pep19-2.5 on the aggregate structure, on the binding thermodynamics, and on the cytokine-inducing activity of LPS were characterized, showing defined aggregate changes, high affinity binding and inhibition of cytokine secretion. The data obtained are suitable to refine our view on the preferences of LPS for non-lamellar structures, representing the highest bioactive forms which can be significantly influenced by the binding with neutralizing peptides such as Pep19-2.5.
authors.affiliation: Forschungszentrum Borstel, LG Biophysik, D-23845 Borstel, Germany. Electronic address: kbrandenburg@fz-borstel.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brandenburg
authors.affiliation: Experimentelle Pathologie, D-23845 Borstel, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Heinbockel
authors.affiliation: Forschungszentrum Borstel, LG Biophysik, D-23845 Borstel, Germany.
authors.forename: Wilmar
authors.initials: W
authors.lastname: Correa
authors.affiliation: National Institute of Advanced Industrial Science and Technology AIST, Takamatsu, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fukuoka
authors.affiliation: Forschungszentrum Borstel, LG Biophysik, D-23845 Borstel, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gutsmann
authors.affiliation: Bioanalytische Chemie, D-23845 Borstel, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.affiliation: European Molecular Biology Laboratory, Hamburg Outstation, EMBL c/o DESY, Notkestr. 85, 22603 Hamburg, Germany.
authors.forename: Michel H J
authors.initials: MH
authors.lastname: Koch
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing / Q000737:chemistry* / Q000276:immunology; D002151:Calorimetry / Q000379:methods; D002478:Cells, Cultured; D004755:Enterobacteriaceae / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000494:pharmacology; D011485:Protein Binding; D053838:Scattering, Small Angle; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D057134:Antibodies, Neutralizing; D008070:Lipopolysaccharides; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha
keywords: Antimicrobial peptides; Cytokines; Endotoxic conformation; Lipopolysaccharides; SAXS