A protein-protein interaction dictates Borrelial infectivity.

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TitleA protein-protein interaction dictates Borrelial infectivity.
Publication TypeJournal Article
Year of Publication2017
AuthorsThakur, M, Sharma, K, Chao, K, Smith, AA, Herzberg, O, Pal, U
JournalSci Rep
Volume7
Issue1
Pagination2932
Date Published2017 Jun 07
ISSN2045-2322
Abstract

Two Borrelia burgdorferi interacting proteins, BB0238 and BB0323, play distinct roles in pathogen biology and infectivity although a significance of their interaction remained enigmatic. Here we identified the polypeptide segment essential for BB0238-BB0323 interaction and examined how it supports spirochete infectivity. We show that the interaction region in BB0323 requires amino acid residues 22-200, suggesting that the binding encompasses discontinuous protein segments. In contrast, the interaction region in BB0238 spans only 11 amino acids, residues 120-130. A deletion of these 11 amino acids neither alters the overall secondary structure of the protein, nor affects its stability or oligomerization property, however, it reduces the post-translational stability of the binding partner, BB0323. Mutant B. burgdorferi isolates producing BB0238 lacking the 11-amino acid interaction region were able to persist in ticks but failed to transmit to mice or to establish infection. These results suggest that BB0238-BB0323 interaction is critical for post-translational stability of BB0323, and that this interaction is important for mammalian infectivity and transmission of B. burgdorferi. We show that saturation or inhibition of BB0238-BB0323 interaction could be studied in a luciferase assay, which could be amenable for future identification of small molecule inhibitors to combat B. burgdorferi infection.

DOI10.1038/s41598-017-03279-7
Alternate JournalSci Rep
PubMed ID28592866
PubMed Central IDPMC5462797