Kaur, Gundeep and Kaundal, Soni and Kapoor, Srajan and Grimes, Jonathan M and Huiskonen, Juha T and Thakur, Krishan Gopal (2018) Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils. Scientific reports, 8 (1). p. 10124. ISSN 2045-2322
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to NPG. |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 18 Mar 2019 16:51 |
| Last Modified: | 18 Mar 2019 16:51 |
| URI: | http://crdd.osdd.net/open/id/eprint/2161 |
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