title: Surface localization determinants of Borrelia OspC/Vsp family lipoproteins.
abstract: The dimeric OspC/Vsp family surface lipoproteins of Borrelia spirochetes are crucial to the transmission and persistence of Lyme borreliosis and tick-borne relapsing fever. However, the requirements for their proper surface display remained undefined. In previous studies, we showed that localization of Borrelia burgdorferi monomeric surface lipoprotein OspA was dependent on residues in the N-terminal "tether" peptide. Here, site-directed mutagenesis of the B. burgdorferi OspC tether revealed two distinct regions affecting either release from the inner membrane or translocation through the outer membrane. Determinants of both of these steps appear consolidated within a single region of the Borrelia turicatae Vsp1 tether. Periplasmic OspC mutants still were able to form dimers. Their localization defect could be rescued by the addition of an apparently structure-destabilizing C-terminal epitope tag but not by coexpression with wild-type OspC. Furthermore, disruption of intermolecular Vsp1 salt bridges blocked dimerization but not surface localization of the resulting Vsp1 monomers. Together, these results suggest that Borrelia OspC/Vsp1 surface lipoproteins traverse the periplasm and the outer membrane as unfolded monomeric intermediates and assemble into their functional multimeric folds only upon reaching the spirochetal surface.
authors: University of Kansas Medical Center, Department of Microbiology, Molecular Genetics and Immunology, Mail Stop 3029, 3025 Wahl Hall West, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors: Ozan S
authors: OS
authors: Kumru
authors: Ryan J
authors: RJ
authors: Schulze
authors: Mykola V
authors: MV
authors: Rodnin
authors: Alexey S
authors: AS
authors: Ladokhin
authors: Wolfram R
authors: WR
authors: Zückert
mesh_terms: D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D025065:Borrelia burgdorferi / Q000235:genetics / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D021382:Protein Sorting Signals; D021381:Protein Transport
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D008074:Lipoproteins; C079616:OspC protein; D021382:Protein Sorting Signals; C121437:Vsp protein, bacterial