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Selectivity among Anti-� Factors by Mycobacterium tuberculosis ClpX Influences Intracellular Levels of Extracytoplasmic Function � Factors

Joshi, AC and Kaur, P and Nair, RK and Lele, DS and Nandicoori, VK and Gopal, B (2019) Selectivity among Anti-� Factors by Mycobacterium tuberculosis ClpX Influences Intracellular Levels of Extracytoplasmic Function � Factors. In: Journal of bacteriology, 201 (6).

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Official URL: https://dx.doi.org/10.1128/JB.00748-18


Extracytoplasmic function � factors that are stress inducible are often sequestered in an inactive complex with a membrane-associated anti-� factor. Mycobacterium tuberculosis membrane-associated anti-� factors have a small, stable RNA gene A (ssrA)-like degron for targeted proteolysis. Interaction between the unfoldase, ClpX, and a substrate with an accessible degron initiates energy-dependent proteolysis. Four anti-� factors with a mutation in the degron provided a set of natural substrates to evaluate the influence of the degron on degradation strength in ClpX-substrate processivity. We note that a point mutation in the degron (X-Ala-Ala) leads to an order-of-magnitude difference in the dwell time of the substrate on ClpX. Differences in ClpX/anti-� interactions were correlated with changes in unfoldase activities. Green fluorescent protein (GFP) chimeras or polypeptides with a length identical to that of the anti-� factor degron also demonstrate degron-dependent variation in ClpX activities. We show that degron-dependent ClpX activity leads to differences in anti-� degradation, thereby regulating the release of free � from the �/anti-� complex. M. tuberculosis ClpX activity thus influences changes in gene expression by modulating the cellular abundance of ECF � factors.IMPORTANCE The ability of Mycobacterium tuberculosis to quickly adapt to changing environmental stimuli occurs by maintaining protein homeostasis. Extracytoplasmic function (ECF) � factors play a significant role in coordinating the transcription profile to changes in environmental conditions. Release of the � factor from the anti-� is governed by the ClpXP2P1 assembly. M. tuberculosis ECF anti-� factors have an ssrA-like degron for targeted degradation. A point mutation in the degron leads to differences in ClpX-mediated proteolysis and affects the cellular abundance of ECF � factors. ClpX activity thus synchronizes changes in gene expression with environmental stimuli affecting M. tuberculosis physiology. Copyright © 2019 American Society for Microbiology.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to NLM (Medline)
Department/Centre: Division of Biological Sciences > Molecular Biophysics Unit
Depositing User: Id for Latest eprints
Date Deposited: 08 Apr 2019 11:17
Last Modified: 08 Apr 2019 11:17
URI: http://eprints.iisc.ac.in/id/eprint/61998

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