Article
Microbiology
Jinki Yeom, Eduardo A. Groisman
Summary: In Salmonella enterica serovar Typhimurium, the regulation of proteolysis specificity by the HspQ protein and the PhoP regulator in response to low cytoplasmic Mg2+ plays a critical role in controlling protein synthesis and antibiotic persistence.PhoP is a transcriptional regulator that governs proteostasis, and its activation in low cytoplasmic Mg2+ condition impacts the abundance of preexisting proteins by affecting the Lon and ClpAP proteases and their substrates. This mechanism is conserved in enteric bacteria and provides insights into bacterial adaptation to changing environmental conditions.
JOURNAL OF BACTERIOLOGY
(2021)
Article
Multidisciplinary Sciences
Brian D. Reed, Michael J. Meyer, Valentin Abramzon, Omer Ad, Pat Adcock, Faisal R. Ahmad, Gun Alppay, James A. Ball, James Beach, Dominique Belhachemi, Anthony Bellofiore, Michael Bellos, Juan Felipe Beltran, Andrew Betts, Mohammad Wadud Bhuiya, Kristin Blacklock, Robert Boer, David Boisvert, Norman D. Brault, Aaron Buxbaum, Steve Caprio, Changhoon Choi, Thomas D. Christian, Robert Clancy, Joseph Clark, Thomas Connolly, Kathren Fink Croce, Richard Cullen, Mel Davey, Jack Davidson, Mohamed M. Elshenawy, Michael Ferrigno, Daniel Frier, Saketh Gudipati, Stephanie Hamill, Zhaoyu He, Sharath Hosali, Haidong Huang, Le Huang, Ali Kabiri, Gennadiy Kriger, Brittany Lathrop, An Li, Peter Lim, Stephen Liu, Feixiang Luo, Caixia Lv, Xiaoxiao Ma, Evan McCormack, Michele Millham, Roger Nani, Manjula Pandey, John Parillo, Gayatri Patel, Douglas H. Pike, Kyle Preston, Adeline Pichard-Kostuch, Kyle Rearick, Todd Rearick, Marco Ribezzi-Crivellari, Gerard Schmid, Jonathan Schultz, Xinghua Shi, Badri Singh, Nikita Srivastava, Shannon F. Stewman, T. R. Thurston, Philip Trioli, Jennifer Tullman, Xin Wang, Yen-Chih Wang, Eric A. G. Webster, Zhizhuo Zhang, Jorge Zuniga, Smita S. Patel, Andrew D. Griffiths, Antoine M. Van Oijen, Michael McKenna, Matthew D. Dyer, Jonathan M. Rothberg
Summary: This study presents a dynamic approach for single-molecule protein sequencing, where single peptides are probed in real time using a mixture of dye-labeled amino acid recognizers and simultaneously cleaved by aminopeptidases. The peptide sequence is identified by measuring fluorescence intensity, lifetime, and binding kinetics. This method enables discrimination of single amino acid substitutions and posttranslational modifications.
Article
Biochemistry & Molecular Biology
Gabrielle Taylor, Yannick Frommherz, Panagiotis Katikaridis, Dominik Layer, Irmgard Sinning, Marta Carroni, Eilika Weber-Ban, Axel Mogk
Summary: This study investigates the control of ClpC1 activity and how this control is disrupted by the antibacterial drug CymA. It was found that ClpC1 exists in various activity states and CymA can enhance ClpC1 activity and degradation activity towards substrates. The resting state of ClpC1 and the CymA-induced assembly state both rely on interactions between the middle domains of ClpC1. Furthermore, overexpression of this assembly state is toxic to other bacteria.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Haiying Zhang, Silvi Chacko, Joe R. Cannon
Summary: Cyclic peptides are promising therapeutics with the ability to disrupt protein-protein interactions and flexibility in screening strategies. However, their identification in metabolite analysis poses challenges. To address the issue of soft spot identification, a derivatization method using 2-pyridine carboxaldehyde was employed and demonstrated on a whole cell lysate digest. This approach effectively reduces the hit-to-lead time for generating proteolytically stable peptide candidates.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Computer Science, Hardware & Architecture
Xi-Jun Lin, Qihui Wang, Lin Sun, Zhen Yan, Peishun Liu
Summary: The proposed certificateless proxy signature scheme is unable to defend against malicious-but-passive key generation center (MKGC) attacks as adversaries can forge valid signatures.
Article
Immunology
Manish Grover, Michael K. Fasseas, Clara Essmann, Kenneth Liu, Christian Braendle, Marie-Anne Felix, Sally L. Glockling, Michalis Barkoulas
Summary: Oomycetes are a group of eukaryotic organisms, with the Haptoglossa genus characterized by specialized gun cells carrying a harpoon-like infection apparatus. In this study, it was found that Haptoglossa species are potent natural pathogens of Caenorhabditis nematodes, causing excessive tissue degradation upon entry in the body cavity while leaving the host cuticle intact. The host transcriptional response to Haptoglossa infection shares similarities with the response against the oomycete Myzocytiopsis humicola, with induction of chitinase-like genes in the hypodermis being a key example of this shared feature.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Michal Ziemski, Julia Leodolter, Gabrielle Taylor, Anne Kerschenmeyer, Eilika Weber-Ban
Summary: In Mtb, the Clp protease degradation pathway is essential for growth and is a promising drug target. Using a BACTH screening approach, protein interaction partners of the ClpC1 chaperone were identified, with a focus on type II toxin-antitoxin systems. Antitoxins from the Vap and Rel families were shown to be degraded by ClpCP in vitro, implicating ClpCP in the N-end rule pathway.
Article
Chemistry, Medicinal
Zehui Zhou, Guizhen Zhou, Chuan Zhou, Zisheng Fan, Rongrong Cui, Yupeng Li, Rui Li, Yuejiao Gu, Huajie Li, Zhiming Ge, Xiaojia Cai, Bing Jiang, Dan Wang, Mingyue Zheng, Tianfeng Xu, Sulin Zhang
Summary: The linker moiety of a PROTAC molecule is crucial for its degradation activity, target selectivity, and physico-chemical properties. Understanding the underlying mechanisms of linker modification is important for enhancing PROTAC degradation and developing novel chemotherapies.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Isadora Louise Alves da Costa Ribeiro Quintans, Juliana Alves da Costa Ribeiro Souza, Michael K. Deyholos
Summary: The causes of fusarium wilt and pasmo in flax (Linum usitatissimum) are Fusarium oxysporum f. sp. lini and Septoria linicola. Alternaria spp., a third fungal genus, has also been found in flax varieties and is a source of spoiling and mycotoxins in crops. The study compared the effectiveness of cyclolinopeptides (CLPs), polyamines (spermidine and spermine), and the fungicide carbendazimin in controlling three fungi (F. oxysporum, S. linicola, and Alternaria spp). The results showed limited antifungal activities of polyamines and CLPs, with spermidine being the most effective compound.
Review
Plant Sciences
Bartosz Adamczyk
Summary: Human activities have accelerated the deterioration of the global nitrogen cycle, mainly due to the overuse of inorganic nitrogen fertilizers in nutrient-limited cropping systems. To prevent further dysregulation of the nitrogen cycle, it is necessary to enhance plant nitrogen use efficiency. This can be achieved by unraveling plant mechanisms for accessing soil nitrogen, particularly the high-molecular-mass nitrogen pool.
Article
Microbiology
Hsueh-Hsia Lo, Hsiao-Ching Chang, Chao-Tsai Liao, Yi-Min Hsiao
Summary: ATP-dependent proteases are essential in bacteria, and in Xanthomonas campestris pv. campestris, two uncharacterized clp genes (clpS and clpA) were found to be temperature-dependent and crucial for heat tolerance and pathogenicity, respectively. This study provides new insights into the functions of clpS and clpA in Xanthomonas.
ANTONIE VAN LEEUWENHOEK INTERNATIONAL JOURNAL OF GENERAL AND MOLECULAR MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Chang Hoon Ji, Hee Yeon Kim, Min Ju Lee, Ah Jung Heo, Daniel Youngjae Park, Sungsu Lim, Seulgi Shin, Woo Seung Yang, Chang An Jung, Kun Young Kim, Eun Hye Jeong, Sun Ho Park, Su Bin Kim, Su Jin Lee, Jeong Eun Na, Ji In Kang, Hyung Min Chi, Hyun Tae Kim, Yun Kyung Kim, Bo Yeon Kim, Yong Tae Kwon
Summary: In this study, the authors develop a targeted protein degradation platform called AUTOTAC to degrade oncoproteins and neurodegeneration-associated proteins via the p62-dependent autophagy-lysosome system.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Chemistry, Multidisciplinary
Marco Cavaco, David Andreu, Miguel A. R. B. Castanho
Summary: Proteolytic stability assessment is seen as a crucial aspect of peptide characterization, with challenges in comparing data due to varying assay methods and reporting styles. Guidelines for better communication among experts are suggested for improved data readability and utilization of peptide stability information.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Multidisciplinary Sciences
Amy M. Weeks, James R. Byrnes, Irene Lui, James A. Wells
Summary: This study utilized a new technology targeting the cell membrane (subtiligase-TM) to efficiently capture cell surface N termini, successfully sequencing 807 N termini and quantifying their changes in response to stimuli inducing proteolytic remodeling of the cell surface proteome. The development of the ASCENT database facilitates exploration of extracellular N termini, promoting a deeper understanding of extracellular protease biology.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Cell Biology
Ji-Ung Jung, Anwesha B. Ghosh, Svetlana Earnest, Staci L. Deaton, Melanie H. Cobb
Summary: The protein kinase WNK1 is involved in maintaining cellular ion homeostasis and its accumulation can lead to familial hypertension. This study investigates the degradation pathways of WNK1 and identifies UBR5 as a regulator of WNK1 protein stability that leads to lysosomal degradation.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jinki Yeom, Eduardo A. Groisman
Summary: In times of nutrient scarcity, microorganisms like Salmonella enterica serovar Typhimurium can preserve functional proteins by inhibiting their degradation, allowing for a rapid return to growth once nutrients become available. This strategy is conserved across different microbial species and facilitates quick recovery from slow-growth states.
Article
Multidisciplinary Sciences
Roberto E. Bruna, Christopher G. Kendra, Eduardo A. Groisman, Mauricio H. Pontes
Summary: Phosphorus is essential for biological molecules in bacteria, but excessive intake can lead to cytoplasmic Mg2+ deficiency, affecting bacterial growth and viability. Bacteria limit Pi uptake to prevent this, showing a regulatory logic based on the connection to cytoplasmic Mg2+ homeostasis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Jinki Yeom, Eduardo A. Groisman
Summary: In Salmonella enterica serovar Typhimurium, the regulation of proteolysis specificity by the HspQ protein and the PhoP regulator in response to low cytoplasmic Mg2+ plays a critical role in controlling protein synthesis and antibiotic persistence.PhoP is a transcriptional regulator that governs proteostasis, and its activation in low cytoplasmic Mg2+ condition impacts the abundance of preexisting proteins by affecting the Lon and ClpAP proteases and their substrates. This mechanism is conserved in enteric bacteria and provides insights into bacterial adaptation to changing environmental conditions.
JOURNAL OF BACTERIOLOGY
(2021)
Review
Microbiology
Eduardo A. Groisman, Alexandre Duprey, Jeongjoon Choi
Summary: The PhoP/PhoQ two-component system is crucial in governing virulence, Mg2+ homeostasis, and resistance to antimicrobial agents in Gram-negative bacteria. The system involves the sensor PhoQ and the transcriptional regulator PhoP, with PhoQ being activated by various signals to promote the phosphorylated state of PhoP. This phosphorylated form controls the expression of hundreds of proteins directly and indirectly, revealing novel forms of signal transduction and the physiological consequences of regulon evolution.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2021)
Review
Biochemistry & Molecular Biology
Alexandre Duprey, Eduardo A. Groisman
Summary: DNA supercoiling is a crucial factor in controlling cellular processes, with similarities and differences across different domains of life. Topoisomerases play a key role in mediating changes in DNA supercoiling.
Article
Biochemistry & Molecular Biology
Jeongjoon Choi, Hubert Salvail, Eduardo A. Groisman
Summary: The study reveals that in Salmonella enterica serovar Typhimurium, the RNA chaperone CspC is essential for activating the master virulence regulator PhoP in mildly acidic pH conditions, while CspE is not necessary. This activation is mediated by the virulence gene ugtL and enhances translation by disrupting mRNA secondary structure.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Genetics & Heredity
Hubert Salvail, Jeongjoon Choi, Eduardo A. Groisman
Summary: Operon organization can lead to the concerted transcription of genes, with some operons producing two mRNAs but only allowing translation of certain genes. In the case of a bicistronic operon involving the novel gene ugtS and the virulence gene ugtL in Salmonella enterica serovar Typhimurium, only the longer mRNA permits translation of both genes. The small protein UgtS plays a role in regulating the virulence program by controlling the phosphorylation kinetics of the master virulence regulator PhoP.
Article
Multidisciplinary Sciences
Jeongjoon Choi, Matias Schmukler, Eduardo A. Groisman
Summary: Horizontal gene transfer drives bacterial evolution, and H-NS proteolysis is a mechanism essential for derepressing foreign genes and colonization of mammalian hosts.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Weiwei Han, Bee-Zen Peng, Chunyan Wang, Guy E. Townsend II, Natasha A. Barry, Frank Peske, Andrew L. Goodman, Jun Liu, Marina Rodnina, Eduardo A. Groisman
Summary: Protein synthesis is a vital cellular process that requires a significant amount of energy. However, cells can sustain protein synthesis under starvation conditions through the use of a bacterial elongation factor called EF-C2, which promotes translocation without hydrolyzing GTP. EF-G2, a variant of EF-C2, is crucial for bacterial gut colonization and can sustain protein synthesis at slower rates. EF-G2 is more abundant than canonical EF-C1 and specifically accumulates during carbon starvation. A unique 26-residue region in EF-G2 is essential for protein synthesis, dissociation from the ribosome, and the absence of GTPase activity. These findings provide insights into how cells minimize energy consumption while maintaining protein synthesis in fluctuating nutrient environments.
Article
Multidisciplinary Sciences
Emilia Krypotou, Guy E. Townsend, Xiaohui Gao, Shoichi Tachiyama, Jun Liu, Nick D. Pokorzynski, Andrew L. Goodman, Eduardo A. Groisman
Summary: Therapeutic manipulation of the gut microbiota has great potential for human health. Bacteria in the gut use phase separation to enhance their fitness and this mechanism can be targeted for clinical intervention. The intrinsically disordered region (IDR) of the transcription termination factor Rho is crucial for phase separation and gene regulation in the gut. Phase separation is vital for host-commensal bacteria interactions and has implications for novel clinical applications.
Article
Biochemistry & Molecular Biology
Eduardo A. A. Groisman, Jeongjoon Choi
Summary: Horizontal gene transfer plays a significant role in bacterial evolution. Enteric bacteria such as Salmonella Typhimurium and Escherichia coli break down the silencing effect of H-NS protein on horizontally acquired genes by using the same protease, Lon, in different environments. Anti-silencing proteins displace H-NS from AT-rich DNA, making H-NS susceptible to degradation and decreasing its overall amounts. The conservation of amino acid sequences in the Lon protease and H-NS cleavage site suggests a common mechanism for exploiting horizontally acquired genes in diverse bacteria.
Review
Microbiology
Nick D. Pokorzynski, Eduardo A. Groisman
Summary: Cells adjust growth and metabolism to nutrient availability. Facultative intracellular pathogens must efficiently prioritize carbon utilization in order to survive in their animal hosts. Bacterial regulators of carbon metabolism control virulence programs, while signals controlling virulence regulators may impact carbon source utilization. Intestinal inflammation and disruption of the gut microbiota can also influence the availability of carbon sources. Coordination between virulence factors and carbon utilization determinants allows pathogens to adopt metabolic pathways that promote antimicrobial resistance and overcome nutrient deprivation imposed by the host.
MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS
(2023)
Article
Gastroenterology & Hepatology
Victoria H. Pearce, Eduardo A. Groisman, Guy E. Townsend II
Summary: The mammalian gut microbiota plays a crucial role in human health and has therapeutic potential for treating various diseases. Dietary factors, particularly simple sugars, can alter the composition of gut microbiota and lead to pathogenic outcomes. This study reveals a molecular pathway through which dietary sugars can silence a key regulator of carbohydrate utilization in gut microbiota, highlighting the potential for targeted interventions in modulating microbial populations for therapeutic purposes.
Correction
Multidisciplinary Sciences
R. J. L. Townshend
Correction
Microbiology
Alexandre Duprey, Eduardo A. Groisman