Article
Multidisciplinary Sciences
Ah Jung Heo, Su Bin Kim, Chang Hoon Ji, Dohyun Han, Su Jin Lee, Su Hyun Lee, Min Ju Lee, Ji Su Lee, Aaron Ciechanover, Bo Yeon Kim, Yong Tae Kwon
Summary: Cellular homeostasis requires sensing and adaptation to intracellular oxygen and reactive oxygen species. The Arg/N-degron pathway targets proteins for degradation through oxidation, arginylation, and ubiquitylation. Proteins may be partially stabilized under acute hypoxia, but can be chemically oxidized by ROS to generate a lysosomal N-degron under prolonged hypoxia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Kha The Nguyen, Shinyeong Ju, Sang-Yoon Kim, Chang-Seok Lee, Cheolju Lee, Cheol-Sang Hwang
Summary: Ubiquitin can undergo N-terminal modifications, including N-terminal methionine excision, N-terminal deamination, and N-terminal arginylation. N-terminal arginylation of ubiquitin and its conjugated proteins are upregulated during the stationary-growth phase or under oxidative stress. This discovery expands the complexity of the ubiquitin code.
MOLECULES AND CELLS
(2022)
Article
Biochemistry & Molecular Biology
Xiao Liang, Jun Xiao, Xuzichao Li, Yujie Liu, Yao Lu, Yanan Wen, Zexing Li, Xing Che, Yongjian Ma, Xingyan Zhang, Yi Zhang, Deng Jian, Peihui Wang, Chenghao Xuan, Guimei Yu, Long Li, Heng Zhang
Summary: The E3 ligase TRIM7 plays a critical role in viral infection and pathogenesis. The association between TRIM7 and its substrates is determined by the C-terminal glutamine residue of 2C peptides. New substrates of TRIM7, including norovirus and SARS-CoV-2 proteins, have been identified. Crystal structures of TRIM7 in complex with peptides from SARS-CoV-2 proteins reveal a common recognition mode.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yao Li, Yueling Zhao, Xiaojie Yan, Chen Ye, Sara Weirich, Bing Zhang, Xiaolu Wang, Lili Song, Chenhao Jiang, Albert Jeltsch, Cheng Dong, Wenyi Mi
Summary: The N-degron pathway is important for maintaining protein homeostasis. This study reveals that ZER1 and ZYG11B can recognize small N-terminal residues other than glycine. N-terminal serine, alanine, and cysteine undergo N-terminal acetylation, mediated by N-terminal acetyltransferase (NAT), which prevents their recognition by ZER1/ZYG11B. The crystal structures of ZER1 and ZYG11B bound to various non-acetylated small N-terminal residues provide insights into the mechanism of substrate recognition.
NATURE COMMUNICATIONS
(2022)
Review
Oncology
Mohamed A. Eldeeb
Summary: In mammalian cells, intracellular protein degradation is mediated selectively by the Ubiquitin-Proteasome System (UPS) and autophagic-lysosomal system. Recent advances have shown the potential therapeutic implications of targeting N-degron proteolytic pathways to sensitize cancer cells to chemotherapeutic agents and inhibit growth of breast cancer cells. UPS-mediated protein degradation plays a crucial role in regulating cellular processes such as cell division, differentiation, and demise.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Miho Sakato-Antoku, Jeremy L. Balsbaugh, Stephen M. King
Summary: Axonemal dyneins, the microtubule motors powering ciliary motility, undergo complex processing and assembly pathways in the cytoplasm. This study provides insights into the N-terminal processing patterns of dynein heavy chains and identifies acetylase complexes involved in this process. Furthermore, the study reveals the potential role of an unmodified Pro residue in directing the cytosolic stoichiometry of other dynein complex subunits.
Article
Microbiology
Vivek Gurung, Indranil Biswas
Summary: Regulated proteolysis plays a vital role in streptococci by facilitating degradation of misfolded and native regulatory proteins. Through preliminary proteomic analysis, we identified potential ClpX substrates in Streptococcus mutans. Our study reveals the species-specific recognition and internal motif recognition capability of ClpX in streptococci.
JOURNAL OF BACTERIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dianela Aguilar Lucero, Alejo Cantoia, Carolina Sanchez-Lopez, Andres Binolfi, Axel Mogk, Eduardo A. Ceccarelli, German L. Rosano
Summary: In the N-degron pathway of protein degradation, ClpS1 in chloroplasts recognizes substrates based on canonical residues and undergoes local remodeling upon substrate binding. This study supports the existence of a chloroplastic N-degron pathway.
Article
Biochemistry & Molecular Biology
Stephen A. Peter, Jessica S. Isaac, Franz Narberhaus, Julia E. Weigand
Summary: Proteome integrity is crucial for cellular homeostasis and adaptation to stress conditions like hypoxia, with alternative splicing being a mechanism for rapid adaptation. The isoE degron, generated under hypoxia, represents a universal protein degradation signal functional in mammalian cells, yeast, and bacteria. The conserved (F/W)xxW motif is essential for efficient protein decay mediated by the proteasome in eukaryotes and Lon protease in bacteria.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Plant Sciences
Aida Kozlic, Nikola Winter, Theresia Telser, Jakob Reimann, Katrin Rose, Lilian Nehlin, Sophie Berckhan, Gunjan Sharma, Charlene Dambire, Tinne Boeckx, Michael J. Holdsworth, Andreas Bachmair
Summary: The N-degron pathway is a branch of the ubiquitin-proteasome system that uses amino-terminal residues as degradation signals. This study reconstituted part of the plant N-degron pathway by expressing two enzymes from Arabidopsis thaliana in a mutated Saccharomyces cerevisiae strain. A novel assay was developed to monitor the stability of GFP-linked plant proteins with Arginine N-degrons.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Multidisciplinary Sciences
Sheng Shu, Wei Mi
Summary: This study elucidates some regulatory mechanisms involving essential membrane proteins LapB and YejM, with LPS levels controlling the formation of the YejM/LapB complex to determine LpxC protein levels.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Sang Mi Shim, Ha Rim Choi, Soon Chul Kwon, Hye Yeon Kim, Ki Woon Sung, Eui Jung Jung, Su Ran Mun, Tae Hyun Bae, Dong Hyun Kim, Yeon Sung Son, Chan Hoon Jung, Jihoon Lee, Min Jae Lee, Joo-Won Park, Yong Tae Kwon
Summary: The N-degron pathway regulates the autophagic degradation of damaged peroxisomal fragments by generating an N-degron through oxidation and arginylation of ACAD10. The study suggests that inhibiting ATE1 R-transferases with tannic acid may have potential as a treatment for peroxisome biogenesis disorders.
Article
Biochemistry & Molecular Biology
Juhee P. Morehouse, Tania A. Baker, Robert T. Sauer
Summary: AAA+ proteolytic machines are essential for maintaining the cellular proteome. In Escherichia coli, FtsH, a unique AAA+ protease, degrades both membrane and cytosolic proteins. Surprisingly, FtsH can also degrade a stable protein DHFR without relying on recognition of unstructured polypeptides at the N- or C-terminus. Our findings provide insights into substrate recognition by FtsH and expand its previously reported degradation capacity.
Article
Plant Sciences
Anne-Marie Labandera, Hannah M. Tedds, Mark Bailey, Colleen Sprigg, Ross D. Etherington, Olunwatunmise Akintewe, Geetika Kalleechurn, Michael J. Holdsworth, Daniel J. Gibbs
Summary: VRN2, a subunit of PRC2, is regulated by O-2 and the N-degron pathway, showing differential activity in plant development. Its stability affects flowering and root architecture, with environmental cues influencing its accumulation and function.
Article
Plant Sciences
Daan A. Weits, Lina Zhou, Beatrice Giuntoli, Laura Dalle Carbonare, Sergio Iacopino, Luca Piccinini, Lara Lombardi, Vinay Shukla, Liem T. Bui, Giacomo Novi, Joost T. van Dongen, Francesco Licausi
Summary: N-terminal cysteine oxidases (NCOs) oxidise the N-terminal cysteine of specific proteins, initiating proteolytic N-degron pathway. Both types of PCOs regulate the anaerobic response in angiosperms.
PLANT CELL AND ENVIRONMENT
(2023)
Article
Immunology
Erin R. Murphy, Johanna Rossmanith, Jacob Sieg, Megan E. Fris, Hebaallaha Hussein, Andrew B. Kouse, Kevin Gross, Chunxi Zeng, Jennifer Hines, Franz Narberhaus, Peter W. Coschigano
INFECTION AND IMMUNITY
(2020)
Article
Microbiology
Christian Twittenhoff, Ann Kathrin Heroven, Sabrina Muehlen, Petra Dersch, Franz Narberhaus
Article
Microbiology
Beate Sauerbrei, Jan Arends, Danja Schunemann, Franz Narberhaus
JOURNAL OF BACTERIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Christian Twittenhoff, Vivian B. Brandenburg, Francesco Righetti, Aaron M. Nuss, Axel Mosig, Petra Dersch, Franz Narberhaus
NUCLEIC ACIDS RESEARCH
(2020)
Article
Microbiology
Alexander Kraus, Mareen Weskamp, Jennifer Zierles, Miriam Balzer, Ramona Busch, Jessica Eisfeld, Jan Lambertz, Marc M. Nowaczyk, Franz Narberhaus
JOURNAL OF BACTERIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Jessica Eisfeld, Alexander Kraus, Christian Ronge, Michelle Jagst, Vivian B. Brandenburg, Franz Narberhaus
Summary: The study revealed that the LysR-type regulator VtlR (also known as LsrB) controls the expression of sRNAs including AbcR1 and PmaR, impacting the expression of numerous genes, including ABC transporter genes and other sRNA genes. VtlR/LsrB was identified as the master regulator of many sRNAs, orchestrating the response of cells to environmental conditions by harnessing the regulatory power of sRNAs.
MOLECULAR MICROBIOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Julia Kleetz, Leon Welter, Ann-Sophie Mizza, Meriyem Aktas, Franz Narberhaus
Summary: This study expands our understanding of bacterial phosphatidylcholine (PC) formation through the identification, purification, and characterization of Pmts from phylogenetically diverse thermophilic bacteria. Insights into the functional characteristics of Pmt enzymes in thermophilic actinomycetes and proteobacteria are provided.
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Microbiology
Simon Czolkoss, Pia Borgert, Tessa Poppenga, Georg Hoelzl, Meriyem Aktas, Franz Narberhaus
Summary: Some soil-dwelling bacteria have the ability to metabolize exogenous lyso-phospholipids and convert them into non-canonical lipid bis(monoacylglycero)phosphate (BMP), indicating a remarkable adaptive response of bacterial membranes to environmental changes.
ENVIRONMENTAL MICROBIOLOGY
(2021)
Article
Microbiology
Dominik Wuellner, Maren Gesper, Annika Haupt, Xiaofei Liang, Pei Zhou, Pascal Dietze, Franz Narberhaus, Julia E. Bandow
Summary: This study investigated the physiological response of Pseudomonas aeruginosa to various antibiotics, revealing cellular defense strategies and similarities in response profiles. The findings provide insights into the effects of commonly used antibiotics on P. aeruginosa and contribute to the evaluation of novel compounds.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Biotechnology & Applied Microbiology
Julia Kleetz, Georgios Vasilopoulos, Simon Czolkoss, Meriyem Aktas, Franz Narberhaus
Summary: Escherichia coli is a common model bacterium with a membrane composition that can be readily tailored to include non-native lipids such as phosphatidylcholine (PC) for biotechnology applications.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2021)
Article
Microbiology
Stephan Pienkoss, Soheila Javadi, Paweena Chaoprasid, Thomas Nolte, Christian Twittenhoff, Petra Dersch, Franz Narberhaus
Summary: This study explores the temperature-dependent synthesis of the secretion regulator YopN in the foodborne pathogen Yersinia pseudotuberculosis, demonstrating its role in controlling effector protein translocation through the type III secretion system. The research reveals a critical RNA thermometer-mediated regulation of YopN expression at infection-relevant temperatures, highlighting the importance of adjusting cellular concentration of surveillance factors for controlled translocation of virulence factors in bacterial pathogens.
Article
Biochemical Research Methods
Vivian B. Brandenburg, Franz Narberhaus, Axel Mosig
Summary: This study introduces a novel pre-training approach using inverse folding to generate training data, which significantly enhances the performance of neural networks in identifying RNA structural motifs. Through systematic in silico mutagenesis experiments, this method shows great potential in recognizing RNA structural motifs such as intrinsic transcription terminators.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anna-Maria Moeller, Simon Brueckner, Lea-Janina Tilg, Blanka Kutscher, Marc M. Nowaczyk, Franz Narberhaus
Summary: This study investigates the function of the outer membrane (OM) in Gram-negative bacteria and the mechanism of LPS biosynthesis. The results show that LapB is a multi-functional protein that regulates the synthesis of LPS and PL by interacting with key enzymes.
MOLECULAR MICROBIOLOGY
(2023)
Article
Genetics & Heredity
Daniel R. Scheller, Franziska I. Becker, Andrea Wimbert, Dominik D. Meggers, Stephan Pienkoss, Christian D. Twittenhoff, Lisa R. Knoke, Lars I. D. Leichert, Franz Narberhaus
Summary: Pathogenic bacteria like Yersinia pseudotuberculosis encounter reactive oxygen species (ROS) as a defense mechanism in mammalian hosts. In response, the bacteria mount an oxidative stress response. This study analyzes the transcriptional and translational regulation of ROS defense genes by examining RNA structure, gene expression, and enzymatic assays. The results reveal a multilayered regulation and an important role of RNAT-controlled katY expression in the oxidative stress response of Yersinia.
Article
Biochemistry & Molecular Biology
Janka J. Schmidt, Donata C. L. E. Remme, Jessica Eisfeld, Vivian B. Brandenburg, Hannah Bille, Franz Narberhaus
Summary: Agrobacterium tumefaciens is a plant pathogen that exhibits resistance to beta-lactam antibiotics through the regulation of specific genes. In this study, researchers uncovered the important role of the transcriptional regulator LsrB acting upstream of AmpR in inducible resistance.
MOLECULAR MICROBIOLOGY
(2023)