Borrelia burgdorferi, which is the causative agent of Lyme disease, is transmitted from infected Ixodes ticks to a mammalian host following a tick bite. Upon changing the host organism from an Ixodes tick to a warm-blooded mammal, the spirochete must adapt to very different conditions, which is achieved by altering the expression of several genes in response to a changing environment. Recently, considerable attention has been devoted to several outer surface proteins, including BBA73, that undergo dramatic upregulation during the transmission of B. burgdorferi from infected Ixodes ticks to mammals and that are thought to be important for the establishment and maintenance of the infection. These upregulated proteins could reveal the mechanism of pathogenesis and potentially serve as novel drug targets to prevent the transmission of the pathogenic bacteria. To promote effective treatments for Lyme disease and to gain better insight into B. burgdorferi pathogenesis, we have determined the crystal structure of the upregulated outer surface protein BBA73 at 2.0 Å resolution. We observed that the BBA73 protein exists as a homodimer both in the crystal and in solution. The monomers interact with their N-terminal α-helices and form a cleft that could potentially serve as a ligand or receptor binding site. To confirm that the protein dimerizes through the interaction of the N-terminal regions, we produced an N-terminal deletion mutant of BBA73 to disrupt dimerization, and we determined the crystal structure of the truncated BBA73 protein at 1.9 Å resolution. The truncated protein did not form a homodimer, and the crystal structure confirmed that the overall fold is identical to that of the native BBA73 protein. Notably, a paralogous protein CspA from B. burgdorferi with known crystal structure also forms a homodimer, albeit through an entirely different interaction between the monomers.
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