Beyond gene expression: The impact of protein post-translational modifications in bacteria

Cain, Joel A.; Solis, Nestor; Cordwell, Stuart J.

doi:10.1016/j.jprot.2013.08.012

Cited by 168 publications

(134 citation statements)

References 276 publications

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“…Bacteria possess numerous posttranslational mechanisms to regulate essential cellular functions (49). Reversible phosphorylation, the rapid modulation of a target protein through the interplay of protein kinase and phosphatase partners, has been shown to mediate multiple processes in bacteria (15,16,(50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

CTL0511 from Chlamydia trachomatis Is a Type 2C Protein Phosphatase with Broad Substrate Specificity

Claywell

Fisher

2016

J Bacteriol

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Protein phosphorylation has become increasingly recognized for its role in regulating bacterial physiology and virulence. Chlamydia spp. encode two validated Hanks'-type Ser/Thr protein kinases, which typically function with cognate protein phosphatases and appear capable of global protein phosphorylation. Consequently, we sought to identify a Ser/Thr protein phosphatase partner for the chlamydial kinases. CTL0511 from Chlamydia trachomatis L2 434/Bu, which has homologs in all sequenced Chlamydia spp., is a predicted type 2C Ser/Thr protein phosphatase (PP2C). Recombinant maltose-binding protein (MBP)-tagged CTL0511 (rCTL0511) hydrolyzed p-nitrophenyl phosphate (pNPP), a generic phosphatase substrate, in a MnCl 2 -dependent manner at physiological pH. Assays using phosphopeptide substrates revealed that rCTL0511 can dephosphorylate phosphorylated serine (P-Ser), P-Thr, and P-Tyr residues using either MnCl 2 or MgCl 2 , indicating that metal usage can alter substrate preference. Phosphatase activity was unaffected by PP1, PP2A, and PP3 phosphatase inhibitors, while mutation of conserved PP2C residues significantly inhibited activity. Finally, phosphatase activity was detected in elementary body (EB) and reticulate body (RB) lysates, supporting a role for protein dephosphorylation in chlamydial development. These findings support that CTL0511 is a metal-dependent protein phosphatase with broad substrate specificity, substantiating a reversible phosphorylation network in C. trachomatis. IMPORTANCEChlamydia spp. are obligate intracellular bacterial pathogens responsible for a variety of diseases in humans and economically important animal species. Our work demonstrates that Chlamydia spp. produce a PP2C capable of dephosphorylating P-Thr, P-Ser, and P-Tyr and that Chlamydia trachomatis EBs and RBs possess phosphatase activity. In conjunction with the chlamydial Hanks'-type kinases Pkn1 and PknD, validation of CTL0511 fulfills the enzymatic requirements for a reversible phosphoprotein network. As protein phosphorylation regulates important cellular processes, including metabolism, differentiation, and virulence, in other bacterial pathogens, these results set the stage for elucidating the role of global protein phosphorylation in chlamydial physiology and virulence. C hlamydia spp. are obligate intracellular bacterial pathogens that are widely distributed in nature and are responsible for significant diseases in humans and a variety of animals (1, 2). The human-specific pathogen Chlamydia trachomatis is the leading cause of preventable blindness and the most common reportable bacterial sexually transmitted infection both in the United States and worldwide (3, 4). C. trachomatis infections of the conjunctiva and the urogenital tract may lead to chronic diseases, including trachoma, pelvic inflammatory disease, and infertility (1). Further understanding of the physiology of these highly significant pathogens is critical for developing therapeutics and vaccines.While Chlamydia spp. differ in host range and virul...

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Section: Discussionmentioning

confidence: 99%

CTL0511 from Chlamydia trachomatis Is a Type 2C Protein Phosphatase with Broad Substrate Specificity

Claywell

Fisher

2016

J Bacteriol

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“…The same experimental proteomic datasets are also useful in identifying posttranslational modifications (PTMs) on a proteomewide level (5,6). Many cellular proteins undergo appreciable amounts of PTM in response to certain stimuli, and this dynamic process occurs in various cell compartments to dictate the fate and activity of the modified proteins (7). Identification and mapping of PTMs in proteins have been improved dramatically, mainly due to increases in the sensitivity, speed, accuracy, and resolution of mass spectrometry (MS).…”

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confidence: 99%

Proteogenomic analysis and global discovery of posttranslational modifications in prokaryotes

Han

Yang

Chen

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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We describe an integrated workflow for proteogenomic analysis and global profiling of posttranslational modifications (PTMs) in prokaryotes and use the model cyanobacterium Synechococcus sp. PCC 7002 (hereafter Synechococcus 7002) as a test case. We found more than 20 different kinds of PTMs, and a holistic view of PTM events in this organism grown under different conditions was obtained without specific enrichment strategies. Among 3,186 predicted protein-coding genes, 2,938 gene products (>92%) were identified. We also identified 118 previously unidentified proteins and corrected 38 predicted gene-coding regions in the Synechococcus 7002 genome. This systematic analysis not only provides comprehensive information on protein profiles and the diversity of PTMs in Synechococcus 7002 but also provides some insights into photosynthetic pathways in cyanobacteria. The entire proteogenomics pipeline is applicable to any sequenced prokaryotic organism, and we suggest that it should become a standard part of genome annotation projects.proteogenomics | post-translational modifications | cyanobacteria | photosynthesis | Synechococcus

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“…Many cellular proteins undergo appreciable amounts of PTMs in response to certain stimuli, and this dynamic process occurs in various cell compartments to dictate the fate and activity of the modified proteins [98]. However, system-wide identification of multiple PTMs remains a highly challenging task, especially in situations where some reversible PTMs are induced by a particular stimulus and are present for only a short period [13].…”

Section: Global Discovery Of Ptmsmentioning

confidence: 99%

Proteomic analysis of post translational modifications in cyanobacteria

Xiong

Chen

2016

Journal of Proteomics

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Beyond gene expression: The impact of protein post-translational modifications in bacteria

Cited by 168 publications

References 276 publications

CTL0511 from Chlamydia trachomatis Is a Type 2C Protein Phosphatase with Broad Substrate Specificity

CTL0511 from Chlamydia trachomatis Is a Type 2C Protein Phosphatase with Broad Substrate Specificity

Proteogenomic analysis and global discovery of posttranslational modifications in prokaryotes

Proteomic analysis of post translational modifications in cyanobacteria

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