Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils

Abstract CarD is an essential global transcription regulator from Mycobacterium tuberculosis (Mtb) that binds RNA polymerase and activates transcription by stabilizing the transcription initiation complex. Available crystal structures have captured two distinct, monomeric and domain-swapped homodime...

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Autores principales:	Gundeep Kaur, Soni Kaundal, Srajan Kapoor, Jonathan M. Grimes, Juha T. Huiskonen, Krishan Gopal Thakur
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a9492ed5026b4972a6e8434e695cc730
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spelling	oai:doaj.org-article:a9492ed5026b4972a6e8434e695cc7302021-12-02T15:08:38ZMycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils10.1038/s41598-018-28290-42045-2322https://doaj.org/article/a9492ed5026b4972a6e8434e695cc7302018-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-28290-4https://doaj.org/toc/2045-2322Abstract CarD is an essential global transcription regulator from Mycobacterium tuberculosis (Mtb) that binds RNA polymerase and activates transcription by stabilizing the transcription initiation complex. Available crystal structures have captured two distinct, monomeric and domain-swapped homodimeric, oligomeric states of CarD. However, the actual oligomeric state of CarD in solution and its biological relevance has remained unclear. Here, we confirm the presence of the homodimeric state of CarD in solution by using synchrotron-based small-angle X-ray scattering. Furthermore, by using biochemical and biophysical experiments, in addition to mass-spectrometry, transmission electron microscopy, and confocal imaging, we show that CarD is the first soluble cytosolic protein in Mtb which displays the tendency to form amyloid-like fibrils both in vitro as well as in vivo. We demonstrate that the deletion of the fourteen N-terminal residues involved in domain-swapping hampers amyloid formation, thus, suggesting that domain-swapping is crucial in amyloidogenesis. The discovery of the amyloidogenic property of an essential cytosolic global transcription regulator, CarD, in a pathogenic bacteria will further open up new frontiers in research.Gundeep KaurSoni KaundalSrajan KapoorJonathan M. GrimesJuha T. HuiskonenKrishan Gopal ThakurNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Gundeep Kaur Soni Kaundal Srajan Kapoor Jonathan M. Grimes Juha T. Huiskonen Krishan Gopal Thakur Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
description	Abstract CarD is an essential global transcription regulator from Mycobacterium tuberculosis (Mtb) that binds RNA polymerase and activates transcription by stabilizing the transcription initiation complex. Available crystal structures have captured two distinct, monomeric and domain-swapped homodimeric, oligomeric states of CarD. However, the actual oligomeric state of CarD in solution and its biological relevance has remained unclear. Here, we confirm the presence of the homodimeric state of CarD in solution by using synchrotron-based small-angle X-ray scattering. Furthermore, by using biochemical and biophysical experiments, in addition to mass-spectrometry, transmission electron microscopy, and confocal imaging, we show that CarD is the first soluble cytosolic protein in Mtb which displays the tendency to form amyloid-like fibrils both in vitro as well as in vivo. We demonstrate that the deletion of the fourteen N-terminal residues involved in domain-swapping hampers amyloid formation, thus, suggesting that domain-swapping is crucial in amyloidogenesis. The discovery of the amyloidogenic property of an essential cytosolic global transcription regulator, CarD, in a pathogenic bacteria will further open up new frontiers in research.
format	article
author	Gundeep Kaur Soni Kaundal Srajan Kapoor Jonathan M. Grimes Juha T. Huiskonen Krishan Gopal Thakur
author_facet	Gundeep Kaur Soni Kaundal Srajan Kapoor Jonathan M. Grimes Juha T. Huiskonen Krishan Gopal Thakur
author_sort	Gundeep Kaur
title	Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
title_short	Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
title_full	Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
title_fullStr	Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
title_full_unstemmed	Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
title_sort	mycobacterium tuberculosis card, an essential global transcriptional regulator forms amyloid-like fibrils
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/a9492ed5026b4972a6e8434e695cc730
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Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils

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