Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis
Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed 'pupylation', Pup is synthesized with a terminal glutamine, which is deam...
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| Veröffentlicht in: | Molecular microbiology 2010-09, Vol.77 (5), p.1123-1135 |
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| creator | Cerda-Maira, Francisca A Pearce, Michael J Fuortes, Michele Bishai, William R Hubbard, Stevan R Darwin, K. Heran |
| description | Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed 'pupylation', Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by proteasome accessory factor A (PafA). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is not only involved in the deamidation of Pup, but also needed to maintain wild-type steady state levels of pupylated proteins in Mtb. Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins. |
| doi_str_mv | 10.1111/j.1365-2958.2010.07276.x |
| format | Article |
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Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins.</description><identifier>ISSN: 0950-382X</identifier><identifier>EISSN: 1365-2958</identifier><identifier>DOI: 10.1111/j.1365-2958.2010.07276.x</identifier><identifier>PMID: 20636328</identifier><language>eng</language><publisher>Oxford, UK: Oxford, UK : Blackwell Publishing Ltd</publisher><subject>Amidohydrolases - genetics ; Amidohydrolases - metabolism ; Amino Acid Sequence ; Amino Acid Substitution - genetics ; Animals ; Bacteria ; Bacterial Load ; Bacterial Proteins - genetics ; Bacterial Proteins - metabolism ; Bacteriology ; Biochemistry ; Biological and medical sciences ; Disease Models, Animal ; DNA, Bacterial - chemistry ; DNA, Bacterial - genetics ; Fundamental and applied biological sciences. 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Heran</creatorcontrib><title>Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed 'pupylation', Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by proteasome accessory factor A (PafA). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is not only involved in the deamidation of Pup, but also needed to maintain wild-type steady state levels of pupylated proteins in Mtb. Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins.</description><subject>Amidohydrolases - genetics</subject><subject>Amidohydrolases - metabolism</subject><subject>Amino Acid Sequence</subject><subject>Amino Acid Substitution - genetics</subject><subject>Animals</subject><subject>Bacteria</subject><subject>Bacterial Load</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - metabolism</subject><subject>Bacteriology</subject><subject>Biochemistry</subject><subject>Biological and medical sciences</subject><subject>Disease Models, Animal</subject><subject>DNA, Bacterial - chemistry</subject><subject>DNA, Bacterial - genetics</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Lung - microbiology</subject><subject>Mice</subject><subject>Microbiology</subject><subject>Miscellaneous</subject><subject>Models, Molecular</subject><subject>Molecular Sequence Data</subject><subject>Mutagenesis</subject><subject>Mutagenesis, Site-Directed</subject><subject>Mutant Proteins - genetics</subject><subject>Mutant Proteins - metabolism</subject><subject>Mycobacterium tuberculosis</subject><subject>Mycobacterium tuberculosis - genetics</subject><subject>Mycobacterium tuberculosis - metabolism</subject><subject>Prokaryotes</subject><subject>Proteases</subject><subject>Proteins</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Homology, Amino Acid</subject><subject>Spleen - microbiology</subject><subject>Tuberculosis - microbiology</subject><subject>Tuberculosis - pathology</subject><subject>Ubiquitins - genetics</subject><subject>Ubiquitins - metabolism</subject><subject>Virulence</subject><subject>Virulence Factors - genetics</subject><subject>Virulence Factors - metabolism</subject><issn>0950-382X</issn><issn>1365-2958</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkttu1DAQhi0EokvhFcBCQsBFFtuJE-cCJFRxqNQVSFCJO2viOLveZuPUB9q8PU53WQ6-Gcv_55nx-EcIU7Kkab3ZLmle8ozVXCwZSaekYlW5vL2HFkfhPlqQmpMsF-zHCXrk_ZYQmpMyf4hOWAplzsQChZXttYo9OAwD9JM3HtsOh43Go7NX4CYbjMKxMdfRBDNkvbm6k4I2A371NY6vsbLDNq4hGDvgEcLmBiacxNWkbAMqaGfiDofYaJcK2VThMXrQQe_1k0M8RZcfP3w_-5xdfPl0fvb-IlMlyctMKN02vCuagkOtOIiWMMoaolXbaAG06wiDphRtxQquOsF52QGjZd1UVc3qPD9F7_Z5x9jsdKv0EBz0cnRmlx4mLRj5rzKYjVzbn5LVFReEpQQvDwmcvY7aB7kzXum-h0Hb6KVIc-c1rWgin_9Hbm10aaJeVkVdVCIndYKe_t3PsZHf35GAFwcAvIK-czAo4_9wORUksYl7u-duTK-no06JnO0ht3J2gZxdIGd7yDt7yFu5Wp3Pu3T_2f5-B1bC2qUal9_YbA8qBJtH9wsLWros</recordid><startdate>201009</startdate><enddate>201009</enddate><creator>Cerda-Maira, Francisca A</creator><creator>Pearce, Michael J</creator><creator>Fuortes, Michele</creator><creator>Bishai, William R</creator><creator>Hubbard, Stevan R</creator><creator>Darwin, K. Heran</creator><general>Oxford, UK : Blackwell Publishing Ltd</general><general>Blackwell Publishing Ltd</general><general>Blackwell</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>201009</creationdate><title>Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis</title><author>Cerda-Maira, Francisca A ; Pearce, Michael J ; Fuortes, Michele ; Bishai, William R ; Hubbard, Stevan R ; Darwin, K. 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Psychology</topic><topic>Lung - microbiology</topic><topic>Mice</topic><topic>Microbiology</topic><topic>Miscellaneous</topic><topic>Models, Molecular</topic><topic>Molecular Sequence Data</topic><topic>Mutagenesis</topic><topic>Mutagenesis, Site-Directed</topic><topic>Mutant Proteins - genetics</topic><topic>Mutant Proteins - metabolism</topic><topic>Mycobacterium tuberculosis</topic><topic>Mycobacterium tuberculosis - genetics</topic><topic>Mycobacterium tuberculosis - metabolism</topic><topic>Prokaryotes</topic><topic>Proteases</topic><topic>Proteins</topic><topic>Sequence Analysis, DNA</topic><topic>Sequence Homology, Amino Acid</topic><topic>Spleen - microbiology</topic><topic>Tuberculosis - microbiology</topic><topic>Tuberculosis - pathology</topic><topic>Ubiquitins - genetics</topic><topic>Ubiquitins - metabolism</topic><topic>Virulence</topic><topic>Virulence Factors - genetics</topic><topic>Virulence Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cerda-Maira, Francisca A</creatorcontrib><creatorcontrib>Pearce, Michael J</creatorcontrib><creatorcontrib>Fuortes, Michele</creatorcontrib><creatorcontrib>Bishai, William R</creatorcontrib><creatorcontrib>Hubbard, Stevan R</creatorcontrib><creatorcontrib>Darwin, K. 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Heran</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis</atitle><jtitle>Molecular microbiology</jtitle><addtitle>Mol Microbiol</addtitle><date>2010-09</date><risdate>2010</risdate><volume>77</volume><issue>5</issue><spage>1123</spage><epage>1135</epage><pages>1123-1135</pages><issn>0950-382X</issn><eissn>1365-2958</eissn><abstract>Proteins targeted for degradation by the Mycobacterium proteasome are post-translationally tagged with prokaryotic ubiquitin-like protein (Pup), an intrinsically disordered protein of 64 residues. In a process termed 'pupylation', Pup is synthesized with a terminal glutamine, which is deamidated to glutamate by Dop (deamidase of Pup) prior to attachment to substrate lysines by proteasome accessory factor A (PafA). Importantly, PafA was previously shown to be essential to cause lethal infections by Mycobacterium tuberculosis (Mtb) in mice. In this study we show that Dop, like PafA, is required for the full virulence of Mtb. Additionally, we show that Dop is not only involved in the deamidation of Pup, but also needed to maintain wild-type steady state levels of pupylated proteins in Mtb. Finally, using structural models and site-directed mutagenesis our data suggest that Dop and PafA are members of the glutamine synthetase fold family of proteins.</abstract><cop>Oxford, UK</cop><pub>Oxford, UK : Blackwell Publishing Ltd</pub><pmid>20636328</pmid><doi>10.1111/j.1365-2958.2010.07276.x</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Wiley Online Library (Open Access Collection); Free Full-Text Journals in Chemistry |
| subjects | Amidohydrolases - genetics Amidohydrolases - metabolism Amino Acid Sequence Amino Acid Substitution - genetics Animals Bacteria Bacterial Load Bacterial Proteins - genetics Bacterial Proteins - metabolism Bacteriology Biochemistry Biological and medical sciences Disease Models, Animal DNA, Bacterial - chemistry DNA, Bacterial - genetics Fundamental and applied biological sciences. Psychology Lung - microbiology Mice Microbiology Miscellaneous Models, Molecular Molecular Sequence Data Mutagenesis Mutagenesis, Site-Directed Mutant Proteins - genetics Mutant Proteins - metabolism Mycobacterium tuberculosis Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - metabolism Prokaryotes Proteases Proteins Sequence Analysis, DNA Sequence Homology, Amino Acid Spleen - microbiology Tuberculosis - microbiology Tuberculosis - pathology Ubiquitins - genetics Ubiquitins - metabolism Virulence Virulence Factors - genetics Virulence Factors - metabolism |
| title | Molecular analysis of the prokaryotic ubiquitin-like protein (Pup) conjugation pathway in Mycobacterium tuberculosis |
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