Article
Chemistry, Multidisciplinary
Buyan Pan, Sarah M. Gardner, Kollin Schultz, Ryann M. Perez, Sunbin Deng, Marie Shimogawa, Kohei Sato, Elizabeth Rhoades, Ronen Marmorstein, E. James Petersson
Summary: N-terminal acetylation is a modification carried out by N-terminal acetyltransferases, and NatB is a major member of this enzyme family. NatB acetylates α-synuclein (αS), a protein involved in vesicle trafficking, and modulates its binding properties and fibril formation, which plays a role in Parkinson's disease. This study synthesized a bisubstrate inhibitor of NatB and characterized its structure using cryo-electron microscopy (cryo-EM). The study also revealed conformational changes in αS when bound to NatB through single molecule Förster resonance energy transfer (smFRET) and computational modeling, providing valuable strategies for studying challenging structural biology targets.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
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
Xiaodi Gong, Yaqian Huang, Yan Liang, Yundong Yuan, Yuhao Liu, Tongwen Han, Shujia Li, Hengbin Gao, Bo Lv, Xiahe Huang, Eric Linster, Yingchun Wang, Markus Wirtz, Yonghong Wang
Summary: This study identifies HYPK as a positive regulator of NatA activity in rice and demonstrates the critical role of the OsHYPK-NatA complex in coordinating plant development and stress responses.
Article
Multidisciplinary Sciences
Bert van de Kooij, Evert de Vries, Rogier W. Rooswinkel, George M. C. Janssen, Frederique K. Kok, Peter A. van Veelen, Jannie Borst
Summary: The majority of proteins in mammalian cells are modified by N-terminal acetylation, which can have both inhibitory and promoting effects on protein degradation. However, proteome-wide stability measurements did not find a consistent correlation between N-terminal acetylation and protein stability. By analyzing protein stability datasets, it was found that N-terminal acetylation positively correlates with protein stability for GFP, but this correlation does not apply to the entire proteome. Further experiments showed that N-terminal acetylation can affect protein stability through competition with N-terminal ubiquitination, as well as other mechanisms independent of ubiquitination status.
SCIENTIFIC REPORTS
(2023)
Review
Plant Sciences
Thierry Meinnel, Carmela Giglione
Summary: This review discusses the N-terminal modifications and their associated processing machinery in organisms with plastids gained through primary or secondary endosymbiosis. The N-terminus is a frequently modified site of proteins. Drawing primarily from knowledge gained from land plants, this review provides an overview of the modifications that alter protein N-terminal residues and presents updated information about the associated machinery, including the machinery in Archaeplastida. These modifications include various proteolytic events as well as additions of small groups such as acylation, arginylation, and oxidation. The landscape of N-terminal modifications dedicated to plastids is more complex compared to that of mitochondria. In addition, this review extends to plastid-containing Chromalveolata, including Stramenopiles, Apicomplexa, and Rhizaria. A well-conserved machinery, especially in the plastid, is reported. Examination of the two most abundant proteins on Earth, Rubisco and actin, reveals the complexity of N-terminal modification processes. The transfer of genes from the plastid to the nuclear genome during evolution is exemplified by the N-terminus modification machinery, which appears to be one of the latest transferred to the nuclear genome along with crucial major photosynthetic landmarks. This is supported by the greater number of plastid genes in Paulinellidae and red algae, which are the most recent and fossil recipients of primary endosymbiosis.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Biochemistry & Molecular Biology
Petra Van Damme
Summary: N-terminal acetylation catalyzed by NatA, a major acetyltransferase complex, plays a crucial role in protein modification. Knockdown of human NatA resulted in significant reduction in Nt-acetylation of potential targets, including less efficient NatA substrates and some NatE substrates. The deficiency of NatA Nt-acetylation directly affected protein stability of knockdown targets, suggesting its important role in protein regulation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Petra Van Damme, Camilla Osberg, Veronique Jonckheere, Nina Glomnes, Kris Gevaert, Thomas Arnesen, Henriette Aksnes
Summary: N-terminal acetylation of proteins is a conserved modification in eukaryotes, and the yeast Saccharomyces cerevisiae is a valuable model for studying this process. The bulk of N-terminal acetylation in S. cerevisiae is catalyzed by NatA, NatB, and NatC. In this study, the authors identified 57 yeast NatC substrates using a combination of techniques. They also uncovered some non-NatC NAT activity, suggesting redundancy between NatC and NatE/Naa50. Furthermore, the authors demonstrated the evolutionary conservation of NatC from yeast to humans and its potential implications for studying pathogenic variants. Overall, this work provides valuable insights into NatC-mediated N-terminal acetylation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Franziska Mueller, Alexandra Friese, Claudio Pathe, Richard Cardoso da Silva, Kenny Bravo Rodriguez, Andrea Musacchio, Tanja Bange
Summary: This study reveals that by inhibiting the N-α-acetyltransferase NatA, proteins with IBM-like motifs can be transformed into efficient IAP binders, leading to cellular apoptosis. Thus, acetylation of the amino-terminal IBM-like motifs in NatA substrates serves as a protective mechanism against IAPs.
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
Multidisciplinary Sciences
Chien- Yang, Zikun Zhu, Jeffrey J. Jones, Brett Lomenick, Tsui-Fen Chou, Shu-Ou Shan
Summary: This study investigated the impact of PDF inhibition on bacterial physiology through the analyses of transcriptome and proteome in Escherichia coli. The results showed that loss of PDF activity rapidly induces cellular stress responses, especially those associated with protein misfolding and membrane defects, and leads to a global down-regulation of metabolic pathways. Furthermore, the study revealed that PDF inhibition causes rapid membrane hyperpolarization and impaired membrane integrity, indicating that formyl group retention on nascent proteins is the most immediate and primary consequence of plasma membrane disruption.
Article
Biochemical Research Methods
Panyue Chen, Tiago Jose Paschoal Sobreira, Mark C. Hall, Tony R. Hazbun
Summary: The study reanalyzed proteomic datasets to explore the extent of alpha-N-terminal methylation in yeast and humans, finding evidence of canonical and noncanonical sequences being methylated. A unique amino acid frequency pattern was observed for the methylated peptides in yeast and humans, differing from the canonical motif. This study demonstrates the feasibility of using proteomic data for global investigations into alpha-N-terminal methylation.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Chemistry, Medicinal
Youchao Deng, Sunbin Deng, Yi-Hsun Ho, Sarah M. Gardner, Zhi Huang, Ronen Marmorstein, Rong Huang
Summary: The study designed and prepared a series of highly potent NatD bisubstrate inhibitors, showing high specificity towards NatD and strong competitive characteristics, providing a rational path for future inhibitor development.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Veronique Jonckheere, Petra Van Damme
Summary: The study identified a novel proteoform of the evolutionary conserved N-alpha acetyltransferase Naa40p, named Naa40p25, and revealed the differences in cellular localization, translation function, and protein interactions between this proteoform and the canonical Naa40(L) form; Additionally, two new Naa40p substrates were discovered, and Lge1 was confirmed as the first redundant substrate for yNatA and yNatD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wentian Luo, Alison B. Hickman, Pavol Genzor, Rodolfo Ghirlando, Christopher M. Furman, Anna Menshikh, Astrid Haase, Fred Dyda, Matthew H. Wilson
Summary: This study reveals the regulation and structural features of the piggyBac transposon system in mammalian cells using biochemical and cell-based assays, AlphaFold modeling, and protein redesign. The study demonstrates that phosphorylation of the transposase N-terminus and the need for asymmetric transposon ends negatively regulate piggyBac transposition. These findings expand the potential use of piggyBac transposase for genomic applications.
NUCLEIC ACIDS RESEARCH
(2022)
Editorial Material
Cell Biology
Lan Jiang, Tianyun Shen, Xinyuan Wang, Lunzhi Dai, Kefeng Lu, Huihui Li
Summary: Posttranslational modification plays a crucial role in regulating protein functions. The functions and mechanisms of N-terminal acetylation, which occurs on the first amino acids of proteins, in the field of macroautophagy/autophagy are not well understood. Recent studies have shown that the N-terminal acetyltransferase NatB is essential for autophagy and it modifies actin cytoskeleton constituent Act1 and dynamin-like GTPase Vps1, promoting the formation and fusion of autophagosomes.
Review
Biochemistry & Molecular Biology
Carmela Giglione, Thierry Meinnel
Summary: Protein myristoylation is a common modification found in all living organisms, where myristate serves as a molecular anchor for tagged proteins targeting membranes. Activation of myristate to myristoyl coenzyme A is required in eukaryotes, while bacteria use derivatives for conversion. This process allows proteins to travel across membranes and endomembrane networks efficiently.
PROGRESS IN LIPID RESEARCH
(2022)
Article
Plant Sciences
Thomas Asensio, Cyril Dian, Jean-Baptiste Boyer, Frederic Riviere, Thierry Meinnel, Carmela Giglione
Summary: The text introduces the characteristics of protein N-acetyltransferases and a new high-throughput assay that can better understand the substrate specificity and activity of any GNAT.
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Cell Biology
Mary Akinyi Nyonda, Jean-Baptiste Boyer, Lucid Belmudes, Aarti Krishnan, Paco Pino, Yohann Coute, Mathieu Brochet, Thierry Meinnel, Dominique Soldati-Favre, Carmela Giglione
Summary: Acetyl-CoA plays crucial roles in post-translational modification of proteins and cellular metabolism, with AT1 and NAT8 homologs identified in Toxoplasma gondii and Plasmodium berghei parasites, and widespread N-terminal acetylation observed in both species.
JOURNAL OF CELL SCIENCE
(2022)
Review
Plant Sciences
Thierry Meinnel, Carmela Giglione
Summary: This review discusses the N-terminal modifications and their associated processing machinery in organisms with plastids gained through primary or secondary endosymbiosis. The N-terminus is a frequently modified site of proteins. Drawing primarily from knowledge gained from land plants, this review provides an overview of the modifications that alter protein N-terminal residues and presents updated information about the associated machinery, including the machinery in Archaeplastida. These modifications include various proteolytic events as well as additions of small groups such as acylation, arginylation, and oxidation. The landscape of N-terminal modifications dedicated to plastids is more complex compared to that of mitochondria. In addition, this review extends to plastid-containing Chromalveolata, including Stramenopiles, Apicomplexa, and Rhizaria. A well-conserved machinery, especially in the plastid, is reported. Examination of the two most abundant proteins on Earth, Rubisco and actin, reveals the complexity of N-terminal modification processes. The transfer of genes from the plastid to the nuclear genome during evolution is exemplified by the N-terminus modification machinery, which appears to be one of the latest transferred to the nuclear genome along with crucial major photosynthetic landmarks. This is supported by the greater number of plastid genes in Paulinellidae and red algae, which are the most recent and fossil recipients of primary endosymbiosis.
JOURNAL OF EXPERIMENTAL BOTANY
(2022)
Article
Chemistry, Physical
Thierry Meinnel
Summary: This article discusses the importance of the target specificity of enzyme catalysts for the protein posttranslational modification landscape, suggesting that substrate binding affinities are more important than catalytic rate constants. The study provides a basis for comparing different approaches used to identify protein modification targets.
Article
Multidisciplinary Sciences
Pavlina Miklankova, Eric Linster, Jean-Baptiste Boyer, Jonas Weidenhausen, Johannes Mueller, Laura Armbruster, Karine Lapouge, Carolina De La Torre, Willy Bienvenut, Carsten Sticht, Matthias Mann, Thierry Meinnel, Irmgard Sinning, Carmela Giglione, Rudiger Hell, Markus Wirtz
Summary: This study identifies AtHYPK protein as the first in vivo regulator of NatA activity in plants, which interacts with the ribosome-anchoring subunit of NatA and promotes N-terminal acetylation of various substrates. Loss-of-AtHYPK mutants exhibit remarkable resistance to drought stress and resemble the phenotype of NatA-depleted plants. HYPK regulates plant metabolism and development by modulating NatA activity, and plays a critical role in global proteostasis.
Article
Biochemistry & Molecular Biology
Frederic Riviere, Cyril Dian, Remi F. Dutheil, Paul Monassa, Carmela Giglione, Thierry Meinnel
Summary: This study reveals the distinct features and pathways of N-myristoyltransferases (NMTs)-dependent K-myristoylation and G-myristoylation, and suggests that K-myristoylation may result from post-translational events. Additionally, evidence of depletion of proteins with NMT-dependent K-myristoylation motifs in humans is presented.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Editorial Material
Plant Sciences
Patrick Willems, Pitter F. Huesgen, Iris Finkemeier, Emmanuelle Graciet, Thierry Meinnel, Frank Van Breusegem
FRONTIERS IN PLANT SCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Thomas Arnesen, Henriette Aksnes, Carmela Giglione
Summary: Although located at the ends of proteins, N- and C-termini play critical roles in numerous cellular functions. The International Society of Protein Termini (ISPT) has been formed recently, indicating the increasing interest from scientists in this field. The Protein Termini 2022 conference brought together an interdisciplinary community to discuss the impact of protein ends on protein functionality.
TRENDS IN BIOCHEMICAL SCIENCES
(2023)
Article
Plant Sciences
Ross D. Etherington, Mark Bailey, Jean-Baptiste Boyer, Laura Armbruster, Xulyu Cao, Juliet C. Coates, Thierry Meinnel, Markus Wirtz, Carmela Giglione, Daniel J. Gibbs
Summary: This study reveals that Arabidopsis DOA10A-like E3 ligases regulate the turnover of SQUALENE EPOXIDASE 1 independently of the Ac/N-degron pathway. It also shows that DOA10 E3 ligases in Arabidopsis are not major players in the degradation of N-acetylated proteins.
Article
Biochemistry & Molecular Biology
Harold Durufle, Thierry Balliau, Nicolas Blanchet, Adeline Chaubet, Alexandra Duhnen, Nicolas Pouilly, Melisande Blein-Nicolas, Brigitte Mangin, Pierre Maury, Nicolas Bernard Langlade, Michel Zivy
Summary: In this study, the impact of hybridity status on the responses to drought in sunflower was investigated. It was found that hybrids showed better adaptation and more pronounced responses to water deficit at the molecular and eco-physiological levels compared to inbred lines. The presence of more genes and potential defense mechanism in hybrids may explain these differences.
Letter
Plant Sciences
Thierry Meinnel
