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

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Kaur , G , Kaundal , S , Kapoor , S , Grimes , J M , Huiskonen , J T & Thakur , K G 2018 , ' Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils ' , Scientific Reports , vol. 8 , 10124 . https://doi.org/10.1038/s41598-018-28290-4

Title: Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils
Author: Kaur, Gundeep; Kaundal, Soni; Kapoor, Srajan; Grimes, Jonathan M.; Huiskonen, Juha T.; Thakur, Krishan Gopal
Contributor organization: Helsinki Institute of Life Science HiLIFE
Laboratory of Structural Biology
University of Helsinki
Molecular and Integrative Biosciences Research Programme
Date: 2018-07-04
Language: eng
Number of pages: 13
Belongs to series: Scientific Reports
ISSN: 2045-2322
DOI: https://doi.org/10.1038/s41598-018-28290-4
URI: http://hdl.handle.net/10138/237208
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.
Subject: PROTEIN AGGREGATION PREDICTION
RNA-POLYMERASE HOLOENZYME
BIOLOGICAL MACROMOLECULES
CRYSTAL-STRUCTURE
OPEN COMPLEXES
DOMAIN
MECHANISM
PRION
OLIGOMER
REVEALS
1183 Plant biology, microbiology, virology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


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