The Borrelia burgdorferi infection critical BBK13 protein forms large oligomers in the spirochete membrane.

ABSTRACT

Borrelia burgdorferi is the causative agent of Lyme disease, the leading tick-borne illness in the United States. However, due to, in part, to the significant number of proteins of unknown function encoded across the complex fragmented genome, the molecular mechanisms of B. burgdorferi infection remain largely undefined. Previous work identified the virulence determinant gene, bbk13, which is critical for B. burgdorferi's ability to establish a productive disseminated infection. BBK13 is an immunogenic, non-surface exposed protein of unknown function predicted to harbor an N-terminal transmembrane domain and annotated as a member of the SIMPL domain protein superfamily (PF04402). In eukaryotes, SIMPL domain proteins have been shown to contribute to NF-kappa-B signaling but have no known functions in prokaryotes. Herein we investigated the biochemical and biophysical properties of BBK13 toward elucidation of its function. Bioinformatics analysis revealed secondary and tertiary structural homology between BBK13 and two other prokaryotic SIMPL domain proteins for which the crystal structures have been solved, Brucella abortus BP26 and Campylobacter jejuni cjSLP. Furthermore, comparable to BP26, recombinant BBK13 self-assembled into multimeric complexes in vitro and endogenous BBK13 was found in large oligomeric complexes in the spirochete membrane. Together these data suggest that the oligomeric structure of BBK13 may be important for the molecular function of this critical infection protein.