Article
Immunology
Neil G. Rumachik, Stacy A. Malaker, Nicole K. Paulk
Summary: Advances in gene therapy product and process development have improved our understanding of the basic biology of recombinant AAV, with a particular focus on post-translational modifications of the capsid protein. Concerns about immunogenic responses to high doses of systemically administered rAAV have emphasized the importance of cataloging and tracking potentially immunogenic components of vector lots.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Juliane Hermann, Leon Schurgers, Vera Jankowski
Summary: Post-translational modifications play a key role in protein function and disease progression, but their reliable detection and quantification remain a challenge in clinical diagnosis. Mass spectrometry offers a solution, but its clinical translation still faces challenges.
MOLECULAR ASPECTS OF MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Van-An Duong, Onyou Nam, EonSeon Jin, Jong-Moon Park, Hookeun Lee
Summary: Emiliania huxleyi, a cosmopolitan coccolithophore, was studied for the global discovery of post-translational modifications (PTMs) using a three-dimensional separation method combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methylation was found to be the most frequent PTM, with lysine being the most frequently modified amino acid. The number of identified proteins increased by 22.5% after the PTM search, with some proteins showing a significant increase in intensity.
Review
Biochemistry & Molecular Biology
Gengjun Zhu, Lifang Jin, Wanchun Sun, Shuang Wang, Ning Liu
Summary: This review highlights the importance of post-translational modifications (PTMs) in colorectal cancer (CRC) and discusses their role in diagnosis, prognosis, and treatment. The review summarizes the proteomic profiling strategies for key PTMs and describes the methods used to delineate the global landscapes of each PTM. The review also discusses the current status of PTM research in CRC and provides future perspectives on the role of PTM regulation in translational medicine for CRC.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2022)
Review
Biochemical Research Methods
Ethan James Sanford, Marcus Bustamante Smolka
Summary: All cells have pathways to detect and repair DNA damage. Post-translational modifications (PTMs) have become increasingly important in studying the regulation of DNA repair mechanisms. Mass spectrometry-based proteomics has revolutionized the study of PTMs in DNA damage repair, showing that PTMs play a central role in all aspects of DNA damage signaling and repair.
Article
Parasitology
Sebastian Miles, Javier Magnone, Joaquin Garcia-Luna, Sylvia Dematteis, Gustavo Mourglia-Ettlin
Summary: This study provides insights into the post-translational modifications (PTMs) of proteins in E. granulosus s.l., including the identification of new PTMs and the enzymes involved. These findings expand our knowledge on PTMs in platyhelminthes.
Article
Biochemical Research Methods
Runmin Yang, Jingjing Ma, Shu Zhang, Yu Zheng, Lusheng Wang, Daming Zhu
Summary: This study introduces a new storage format called mzMD for MS datasets and presents an algorithm to query this format for summarizing a given data window. Experimental results demonstrate the high speed and stability of mzMD in retrieving high-quality data window summaries.
Article
Biochemical Research Methods
Suresh Poudel, David Vanderwall, Zuo-Fei Yuan, Zhiping Wu, Junmin Peng, Yuxin Li
Summary: A computational pipeline JUMPptm was presented to extract PTMs from unenriched whole proteome. The deep brain proteome of Alzheimer's disease (AD) was analyzed using JUMPptm, revealing dysregulated PTM peptides during AD progression and establishing a valuable pan-PTM profile for AD research.
Review
Biochemistry & Molecular Biology
Ji Woo Park, Matthew D. Tyl, Ileana M. Cristea
Summary: The regulation of mitochondria structure and function is crucial for viral infections. Post-translational modification of mitochondrial proteins plays a critical role in controlling energy metabolism, apoptosis, and immune signaling. Understanding these modifications and their effects is important for the development of therapeutic strategies.
Article
Plant Sciences
Jonas Giese, Juergen Eirich, Dirk Walther, Youjun Zhang, Ines Lassowskat, Alisdair R. Fernie, Marlene Elsaesser, Veronica G. Maurino, Markus Schwarzlaender, Iris Finkemeier
Summary: The transition from dark to light in the diurnal cycle causes significant physiological changes in plant metabolism, which require specific modes of regulation. While the activities of key metabolic enzymes regulated by light-dependent post-translational modifications (PTMs) have been extensively studied at the protein level, a comprehensive understanding of the global dynamics of light-dependent PTMs is lacking. In this study, we investigated the changes in the metabolome and proteome in Arabidopsis rosettes in response to light in a time-dependent manner, focusing on phosphorylation, lysine acetylation, and cysteine-based redox switches. Our findings revealed that over 1700 out of more than 24,000 detected PTM sites were altered during the transition from dark to light, with different compartments showing distinct PTM changes at different timepoints.
Article
Biochemistry & Molecular Biology
Ghaith M. Hamza, Eric Miele, Don M. Wojchowski, Paul Toran, Camilla R. Worsfold, Tamil S. Anthonymuthu, Vladislav B. Bergo, Andrew X. Zhang, Jeffrey C. Silva
Summary: The Affi-BAMS™ epitope-directed affinity bead capture/MALDI MS platform is effective in quantitatively defining complex PTM marks of H3 and H4 histones. The platform achieves a range of >3 orders of magnitude with a technical precision CV of <5%. It can resolve heterogeneous histone N-terminal PTMs with as little as 100 μg of starting material.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Matteo Calligaris, Chun Y. Yang, Simone Bonelli, Donatella Pia Spano, Stephan A. Mueller, Stefan F. Lichtenthaler, Linda Troeberg, Simone D. Scilabra
Summary: Through the use of surface-spanning enrichment with click-sugars (SUSPECS) proteomics, we identified substrates of ADAM15 and/or proteins regulated by the enzyme on the cell surface of chondrocyte-like cells. Silencing ADAM15 led to significant changes in the membrane levels of 13 proteins, all of which were previously unknown to be regulated by ADAM15. Orthogonal techniques were used to validate the effects of ADAM15 on three of these proteins, confirming its role in cartilage homeostasis.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Daniel Salas-Lloret, Roman Gonzalez-Prieto
Summary: Ubiquitination and SUMOylation are dynamic post-translational modifications that regulate cellular processes. The understanding of these modifications has been increased by the development of mass spectrometry-based approaches. This translated article provides a concise overview of the basic mechanisms of ubiquitination and SUMOylation, as well as recent MS-based approaches for specific target identification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Food Science & Technology
Teodora Dukic, Katarina Smiljanic, Jelena Mihailovic, Ivana Prodic, Danijela Apostolovic, Shu-Hua Liu, Michelle M. Epstein, Marianne van Hage, Dragana Stanic-Vucinic, Tanja Cirkovic Velickovic
Summary: This study investigates the impact of peanut roasting on the post-translational modification (PTM) profiles of major peanut allergens. It finds that roasting can induce changes in certain PTMs, and Ara h 1 is the most modified major allergen in both raw and roasted samples.
Review
Chemistry, Multidisciplinary
Bingjie Zhang, Shanshan Li, Wenqing Shui
Summary: G protein-coupled receptors (GPCRs) are a large family of proteins that play significant roles in cellular and physiological responses. Post-translational modifications (PTMs) of GPCRs, such as glycosylation, phosphorylation, ubiquitination and palmitoylation, have important regulatory functions in receptor folding, biosynthesis, trafficking, dimerization and signaling. This review provides an overview of PTMs in GPCRs, focusing on their types, locations, cross talk and dynamic regulation, which can shed light on the molecular basis of GPCRs and contribute to structure-based drug discovery.
FRONTIERS IN CHEMISTRY
(2022)
Article
Oncology
Lukas Leiendecker, Tobias Neumann, Pauline S. Jung, Shona M. Cronin, Thomas L. Steinacker, Alexander Schleiffer, Michael Schutzbier, Karl Mechtler, Thibault Kervarrec, Estelle Laurent, Kamel Bachiri, Etienne Coyaud, Rajmohan Murali, Klaus J. Busam, Babak Itzinger-Monshi, Reinhard Kirnbauer, Lorenzo Cerroni, Eduardo Calonje, Arno Rutten, Frank Stubenrauch, Klaus G. Griewank, Thomas Wiesner, Anna C. Obenauf
Summary: This study reveals the presence of human papillomavirus 42 (HPV42) in 96% of digital papillary adenocarcinoma (DPA), a cancer occurring on fingers and toes. It shows that HPV42, previously considered nononcogenic, behaves similarly to oncogenic, high-risk HPVs. Machine learning analysis indicates that HPV-driven transformation induces a germ cell-like transcriptional program conserved across all HPV-driven cancers, with implications for early detection, diagnosis, and therapy.
Editorial Material
Cell Biology
Jingyue Jia, Fulong Wang, Zambarlal Bhujabal, Ryan Peters, Michal Mudd, Thabata Duque, Lee Allers, Ruheena Javed, Michelle Salemi, Christian Behrends, Brett Phinney, Terje Johansen, Vojo Deretic
Summary: The functions of mammalian Atg8 proteins (mATG8s) go beyond autophagy and also include Atg8ylation. Lysosomal damage induces stress granules (SGs) that inhibit protein translation via EIF2A/eIF2 alpha phosphorylation and promote ATF4-dependent stress response. GABARAPs interact with NUFIP2 and G3BP1, and Atg8ylation is required for their recruitment to damaged lysosomes. The roles of NUFIP2 and G3BP1 in SG formation and MTOR activation are regulated by GABARAP and Atg8ylation.
Article
Ophthalmology
Iman Jalilian, Santoshi Muppala, Maryam Ali, Johnathon D. Anderson, Brett Phinney, Michelle Salemi, Phillip A. Wilmarth, Christopher J. Murphy, Sara M. Thomasy, VijayKrishna Raghunathan
Summary: This study investigates the effects of TGF-beta and ascorbic acid (AA) on the composition and stiffness of the extracellular matrix (ECM) secreted by corneal endothelial cells (CECs). It finds that TGF-beta decreases matrix stiffness while AA modulates the oxidative stress pathway in the matrix. These findings provide insights into the molecular mechanisms of Fuchs endothelial corneal dystrophy (FECD).
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Biochemical Research Methods
Sebastian Dorl, Stephan Winkler, Karl Mechtler, Viktoria Dorfer
Summary: Spectral library search enables more sensitive peptide identification in tandem mass spectrometry experiments, but suffers from limited availability of high-quality libraries and the difficulty of creating decoy spectra for result validation. MS Ana is a new spectral library search engine that addresses these issues by allowing the use of curated or predicted libraries and providing robust false discovery control through its own decoy library generation algorithm. In benchmark tests, MS Ana outperformed database search, achieving 36% more spectrum matches and 4% more proteins identified in single-shot human cell-line data. The quality of result validation was demonstrated through tests on synthetic peptide pools, and the importance of library selection was highlighted by comparing the performance of different publicly available human spectral libraries.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Leonid Serebreni, Lisa-Marie Pleyer, Vanja Haberle, Oliver Hendy, Anna Vlasova, Vincent Loubiere, Filip Nemcko, Katharina Bergauer, Elisabeth Roitinger, Karl Mechtler, Alexander Stark
Summary: Different classes of promoters have distinct mechanisms of transcription initiation, resulting in either focused or dispersed initiation patterns.
Article
Biochemical Research Methods
Alistair R. Hines, Matthew Edgeworth, Paul W. A. Devine, Samuel Shepherd, Nicholas Chatterton, Claire Turner, Kathryn S. Lilley, Xiaoyu Chen, Nicholas J. Bond
Summary: Antibody-drug conjugates (ADCs) have been widely developed, leading to new approvals and improved standard of care for cancer patients. This study describes the development of a mass-spectrometry-based method that can simultaneously monitor four quality attributes of ADCs, providing new insights into their properties and manufacturing processes. The study identified variations in thiol state, N-linked glycosylation, reduction of disulfide bonds, and polypeptide fragmentation in ADCs. The method offers a high-throughput approach to support the development of engineered antibody scaffolds.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2023)
Review
Biochemical Research Methods
Manuel Matzinger, Rupert L. Mayer, Karl Mechtler
Summary: Mapping proteomic fingerprints to transcriptomic data is crucial for understanding gene expression and phenotype. Despite challenges in protein amplification and lack of established gold standard workflows, advances in microfluidics, sample separation, data acquisition, and analysis have improved the analysis of tiny sample amounts. Sensitivity, robustness, and throughput are still urgent needs, and label-free single-cell mass spectrometry is a promising strategy for unbiased quantification. This review focuses on recent advances in label-free single-cell mass spectrometry workflows and provides guidance for method selection and future prospects.
Article
Multidisciplinary Sciences
Andreas Lackner, Michael Mueller, Magdalena Gamperl, Delyana Stoeva, Olivia Langmann, Henrieta Papuchova, Elisabeth Roitinger, Gerhard Duernberger, Richard Imre, Karl Mechtler, Paulina A. A. Latos
Summary: The Erf-NCoR1/2 complex controls trophoblast differentiation by linking signalling with transcriptional repression.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Jaydeep Sidhaye, Philipp Trepte, Natalie Sepke, Maria Novatchkova, Michael Schutzbier, Gerhard Duernberger, Karl Mechtler, Juergen A. Knoblich
Summary: By analyzing the transcriptome and epigenome during human corticogenesis, important gene regulatory networks have been identified. Through the use of human brain organoids, specific transcriptome and proteome analyses were conducted, revealing gene expression modules during cortical development. One module involving mTOR-mediated regulation of translation was investigated, showing that partial inhibition of ribosomal genes translation prevents premature translation of differentiation markers, crucial for maintaining the accuracy of cortical development.
Article
Reproductive Biology
Jessica A. Kinkade, Arun S. Seetharam, Shrikesh Sachdev, Nathan J. Bivens, Brett S. Phinney, Gabriela Grigorean, R. Michael Roberts, Geetu Tuteja, Cheryl S. Rosenfeld
Summary: The fetal brain of the mouse relies on the placenta for serotonin and other factors, and this study suggests that placental extracellular vesicles (EV) may transport these factors to the developing brain. Analysis of EV from trophoblast cells in mice revealed high levels of serotonin, as well as dopamine and norepinephrine. Additionally, EV from different sources contained different types of small RNA. Furthermore, exposure to EV led to changes in the transcriptome profiles of neural progenitor cells, particularly affecting transcripts enriched in neural tissues.
BIOLOGY OF REPRODUCTION
(2023)
Article
Biochemistry & Molecular Biology
Marwa Zafarullah, Jie Li, Michelle R. Salemi, Brett S. Phinney, Blythe P. Durbin-Johnson, Randi Hagerman, David Hessl, Susan M. Rivera, Flora Tassone
Summary: FXTAS is a neurodegenerative disorder associated with the FMR1 premutation. By analyzing the proteome of premutation carriers, researchers have identified differentially expressed proteins and dysregulated metabolic pathways associated with FXTAS. This provides clues for early diagnosis, development, and progression of FXTAS, as well as the study of related pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Rasheed O. Sule, Brett S. Phinney, Michelle R. Salemi, Aldrin V. Gomes
Summary: Prometryn, a widely used herbicide, has been found to have effects on the cardiac system. Proteomic profiling revealed that prometryn may induce mitochondrial dysfunction and alter signaling pathways related to energy metabolism, protein degradation, and fatty acid metabolism in the heart.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Micha J. J. Birklbauer, Manuel Matzinger, Fraenze Mueller, Karl Mechtler, Viktoria Dorfer
Summary: In the paper "Cross-linking Mass Spectrometry 2.0", the authors present an updated version of the MS Annika search engine, which accurately identifies cross-linked peptides and introduces a novel scoring function. The evaluation shows that MS Annika 2.0 outperforms other search engines in terms of true unique cross-link detection and false discovery rate estimation.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Toxicology
Lo-Wei Lin, Blythe P. Durbin-Johnson, David M. Rocke, Michelle Salemi, Brett S. Phinney, Robert H. Rice
Summary: This study focuses on the effects of environmental pro-oxidants on the formation and protein composition of epidermal cornified envelopes (CEs). The results show that pro-oxidants can alter the CE proteome and that the cellular redox state plays an important role in CE formation.
TOXICOLOGICAL SCIENCES
(2023)
Article
Multidisciplinary Sciences
Nicola M. Moloney, Konstantin Barylyuk, Eelco Tromer, Oliver M. Crook, Lisa M. Breckels, Kathryn S. Lilley, Ross F. Waller, Paula MacGregor
Summary: This study maps the spatial proteomes of two African trypanosome species, Trypanosoma brucei and Trypanosoma congolense, providing insights into the molecular basis for diversity within and between these pathogen species. Comparative analysis reveals key routes of parasitic adaptation to different biological niches.
NATURE COMMUNICATIONS
(2023)
