| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Gygi, Steven P. Bai, Lin Hu, Kuan Chatterjee, Champak Darwin, K. Heran Huang, Jessica Jastrab, Jordan B. Murphy, J. Patrick Wang, Tong Merkx, Remco Ovaa, Huib Li, Huilin |
| Description |
Author Affiliation: Jastrab JB ( Department of Microbiology, New York University School of Medicine, New York, NY 10016); Wang T ( Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973); Murphy JP ( Department of Cell Biology, Harvard Medical School, Boston, MA 02115); Bai L ( Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973); Hu K ( Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973); Merkx R ( Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands); Huang J ( Department of Chemistry, University of Washington, Seattle, WA 98195.); Chatterjee C ( Department of Chemistry, University of Washington, Seattle, WA 98195.); Ovaa H ( Division of Cell Biology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands); Gygi SP ( Department of Cell Biology, Harvard Medical School, Boston, MA 02115); Li H ( Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973); Darwin KH ( Department of Microbiology, New York University School of Medicine, New York, NY 10016); |
| 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 can contribute to the virulence of one the world's most devastating pathogens. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
14 |
| Volume Number |
112 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2015-04-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Mycobacterium Tuberculosis Genetics Proteasome Endopeptidase Complex Chemistry Virulence Adenosine Triphosphate Amino Acid Motifs Amino Acid Sequence Animals Bacterial Proteins Binding Sites Escherichia Coli Metabolism Heat-Shock Proteins Hot Temperature Mice Mice, Inbred C57BL Molecular Sequence Data Pathogenicity Peptides Promoter Regions, Genetic Protein Structure, Tertiary RNA Recombinant Proteins Tuberculosis Microbiology Ubiquitin Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
