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Structural investigations into the interaction of hemoglobin and part structures with bacterial endotoxinsForschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany
Institut für Physikalische Chemie, Martin-Luther-Universität Halle-Wittenberg, Halle (Saale), Germany
European Molecular Biology Laboratory, c/o DESY, Hamburg, Germany
Elektronenmikroskopisches Zentrum der Medizinischen Fakultät, Friedrich-Schiller-Universität Jena, Jena, Germany
Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany
Institute de Biochemie, Université de Lausanne, Lausanne, Switzerland
Institute de Biochemie, Université de Lausanne, Lausanne, Switzerland
Clinique La Prairie, Montreux, Switzerland
Department of Surgery and Immunology, University Health Network, Toronto, Canada
Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany
Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany
Clinique La Prairie, Montreux, Switzerland
Leibniz-Gemeinschaft, Berlin, Germany
Forschungszentrum Borstel, Leibniz-Zentrum für Medizin und Biowissenschaften, Borstel, Germany, Kbranden{at}fz-borstel.de
An understanding of details of the interaction mechanisms of bacterial endotoxins (lipopolysaccharide, LPS) with the oxygen transport protein hemoglobin is still lacking, despite its high biological relevance. Here, a biophysical investigation into the endotoxin:hemoglobin interaction is presented which comprises the use of various rough mutant LPS as well as free lipid A; in addition to the complete hemoglobin molecule from fetal sheep extract, also the partial structure
Key Words: Hemoglobin • endotoxin • lipid A • FTIR • SAXS • phase transition
Innate Immunity, Vol. 14, No. 1,
39-49 (2008) |
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-chain and the heme-free sample are studied. The investigations comprise the determination of the gel-to-liquid crystalline phase behaviour of the acyl chains of LPS, the ultrastructure (type of aggregate structure and morphology) of the endotoxins, and the incorporation of the hemoglobins into artificial immune cell membranes and into LPS. Our data suggest a model for the interaction between Hb and LPS in which hemoglobins do not react strongly with the hydrophilic or with the hydrophobic moiety of LPS, but with the complete endotoxin aggregate. Hb is able to incorporate into LPS with the longitudinal direction parallel to the lipid A double-layer. Although this does not lead to a strong disturbance of the LPS acyl chain packing, the change of the curvature leads to a slightly conical molecular shape with a change of the three-dimensional arrangement from unilamellar into cubic LPS aggregates. Our previous results show that cubic LPS structures exhibit strong endotoxic activity. The property of Hb on the physical state of LPS described here may explain the observation of an increase in LPS-mediating endotoxicity due to the action of Hb.