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Louse-borne relapsing fever, caused by Borrelia recurrentis, provides one of the best documented examples of the causative role of tumor necrosis factor (TNF) in the pathology of severe infection in humans. We have identified the principal TNF-inducing factor of B. recurrentis as a variable major lipoprotein (Vmp). Here we report the complete gene sequence of Vmp, including its lipoprotein leader sequence. Using metabolically labeled forms of the native Vmp we confirm that the TNF inducing properties are associated with the lipid portion of the molecule. Quadrupole orthogonal time of flight mass spectrometry unequivocally locates the lipidic moiety at the NH(2)-terminal cysteine of the native polypeptide, and indicates the existence of three forms which are consistent with the structures C16:0, C16:0, C16:0 glyceryl cysteine; C18:1, C16:0, C16:0 glyceryl cysteine; and C18:0, C16:0, C16:0 glyceryl cysteine. These data provide the first direct evidence that the TNF inducing lipid modification of native Borrelia lipoproteins is a structural homologue of the murein lipoprotein of Escherichia coli.

Original publication




Journal article


The Journal of biological chemistry

Publication Date





937 - 941


University Department of Paediatrics, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom.


Monocytes, Cell Line, Humans, Borrelia, Relapsing Fever, Inflammation, Trypsin, Lipoproteins, Tumor Necrosis Factor-alpha, Peptide Fragments, Bacterial Outer Membrane Proteins, Antigens, Surface, Chromatography, High Pressure Liquid, Mass Spectrometry