A protein-protein interaction dictates Borrelial infectivity

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 s...

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Autores principales:	Meghna Thakur, Kavita Sharma, Kinlin Chao, Alexis A. Smith, Osnat Herzberg, Utpal Pal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b4aaa1be98f4ace9468db80de464f18
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spelling	oai:doaj.org-article:3b4aaa1be98f4ace9468db80de464f182021-12-02T15:06:08ZA protein-protein interaction dictates Borrelial infectivity10.1038/s41598-017-03279-72045-2322https://doaj.org/article/3b4aaa1be98f4ace9468db80de464f182017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03279-7https://doaj.org/toc/2045-2322Abstract 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.Meghna ThakurKavita SharmaKinlin ChaoAlexis A. SmithOsnat HerzbergUtpal PalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Meghna Thakur Kavita Sharma Kinlin Chao Alexis A. Smith Osnat Herzberg Utpal Pal A protein-protein interaction dictates Borrelial infectivity
description	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.
format	article
author	Meghna Thakur Kavita Sharma Kinlin Chao Alexis A. Smith Osnat Herzberg Utpal Pal
author_facet	Meghna Thakur Kavita Sharma Kinlin Chao Alexis A. Smith Osnat Herzberg Utpal Pal
author_sort	Meghna Thakur
title	A protein-protein interaction dictates Borrelial infectivity
title_short	A protein-protein interaction dictates Borrelial infectivity
title_full	A protein-protein interaction dictates Borrelial infectivity
title_fullStr	A protein-protein interaction dictates Borrelial infectivity
title_full_unstemmed	A protein-protein interaction dictates Borrelial infectivity
title_sort	protein-protein interaction dictates borrelial infectivity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b4aaa1be98f4ace9468db80de464f18
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A protein-protein interaction dictates Borrelial infectivity

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