An adenosine triphosphate-independent proteasome activator contributes to the virulence of Mycobacterium tuberculosis

Proceedings of the National Academy of Sciences of the United States of America
Jordan B JastrabK Heran Darwin

Abstract

Mycobacterium tuberculosis encodes a proteasome that is highly similar to eukaryotic proteasomes and is required to cause lethal infections in animals. The only pathway known to target proteins for proteasomal degradation in bacteria is pupylation, which is functionally analogous to eukaryotic ubiquitylation. However, evidence suggests that the M. tuberculosis proteasome contributes to pupylation-independent pathways as well. To identify new proteasome cofactors that might contribute to such pathways, we isolated proteins that bound to proteasomes overproduced in M. tuberculosis and found a previously uncharacterized protein, Rv3780, which formed rings and capped M. tuberculosis proteasome core particles. Rv3780 enhanced peptide and protein degradation by proteasomes in an adenosine triphosphate (ATP)-independent manner. We identified putative Rv3780-dependent proteasome substrates and found that Rv3780 promoted robust degradation of the heat shock protein repressor, HspR. Importantly, an M. tuberculosis Rv3780 mutant had a general growth defect, was sensitive to heat stress, and was attenuated for growth in mice. Collectively, these data demonstrate that ATP-independent proteasome activators are not confined to eukaryotes and ...Continue Reading

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Citations

Nov 4, 2015·Trends in Microbiology·Marie I Samanovic, K Heran Darwin
Mar 24, 2016·Proceedings of the National Academy of Sciences of the United States of America·Lin BaiHuilin Li
Oct 22, 2015·Annual Review of Microbiology·Jordan B Jastrab, K Heran Darwin
Dec 16, 2016·Microbiology and Molecular Biology Reviews : MMBR·Samuel H Becker, K Heran Darwin
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Apr 13, 2017·FEMS Microbiology Reviews·Davide Roncarati, Vincenzo Scarlato
Apr 11, 2019·Frontiers in Molecular Biosciences·Jin GanHuib Ovaa
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Aug 5, 2017·Frontiers in Molecular Biosciences·Adnan Ali H Alhuwaider, David Andrew Dougan
Nov 23, 2020·Current Opinion in Structural Biology·Shoshanna C Kahne, K Heran Darwin
Jan 21, 2021·Antimicrobial Agents and Chemotherapy·Marissa B GuzzoLiem Nguyen
May 1, 2021·The Journal of Biological Chemistry·Yanting YinHuilin Li
Jun 3, 2021·Frontiers in Molecular Biosciences·Patricia Bordes, Pierre Genevaux

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