Article
Chemistry, Analytical
Yue Sun, Yu Liang, Chao Wang, Baofeng Zhao, Zhen Liang, Xiaodan Zhang, Yukui Zhang, Lihua Zhang
Summary: Comprehensive characterization of membrane proteins at the level of proteoforms in complex biological samples by top-down mass spectrometry (MS) is of vital importance in revealing their precise functions. However, severe peak broadening in the separation of hydrophobic membrane proteins, caused by resistance to mass transfer and strong adsorption on separation materials, leads to MS spectra overlap and signal suppression, which makes against the in-depth research on membrane proteoforms.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Vyacheslav Akimov, Mirjam Fehling-Kaschek, Inigo Barrio-Hernandez, Michele Puglia, Jakob Bunkenborg, Mogens M. Nielsen, Jens Timmer, Joern Dengjel, Blagoy Blagoev
Summary: Receptor tyrosine kinases (RTK) play crucial roles in cell proliferation and differentiation by binding growth factors, with EGFR being a prototypic RTK that can bind multiple ligands. A proteomics-based workflow combined with mathematical modeling revealed that ligand-specific ubiquitination events on EGFR play a significant role in signal attenuation and termination. The absolute magnitude of EGFR ubiquitination, rather than distinctly regulated ubiquitination sites, is a major determinant for signal attenuation and subsequent cellular outcomes.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nicolai Bjodstrup Palstrom, Rune Matthiesen, Lars Melholt Rasmussen, Hans Christian Beck
Summary: The human plasma proteome reflects the physiological state of the cardiovascular system and has been used to analyze plasma biomarkers for cardiovascular diseases for decades. However, current plasma biomarkers only address a limited subset of cardiovascular diseases, and there is an urgent need for biomarkers for diseases with increasing incidence like heart failure and abdominal aortic aneurysm. Recent advancements in technologies for analyzing the human plasma proteome are addressing the complexity and facilitating the discovery of novel biomarkers for cardiovascular diseases.
Article
Biochemical Research Methods
Dahang Yu, Zhe Wang, Kellye A. Cupp-Sutton, Yanting Guo, Qiang Kou, Kenneth Smith, Xiaowen Liu, Si Wu
Summary: A top-down TMT MS platform for confidently identifying and quantifying low molecular weight intact proteoforms in complex biological samples was developed by combining filter-SEC technique with high-performance size exclusion chromatography. This technique enables high-throughput analysis of intact proteoforms from Escherichia coli cell lysates, representing the first high-throughput TMT labeling-based, quantitative, top-down MS analysis suitable for complex biological samples.
JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
(2021)
Review
Virology
Yogy Simanjuntak, Kira Schamoni-Kast, Alice Grun, Charlotte Uetrecht, Pietro Scaturro
Summary: This article discusses the harm caused by RNA viruses in human diseases and the latest research progress in revealing RNA virus replication and pathogenesis through mass spectrometry technology. Viruses often impact host functions and induce pathological functional abnormalities, and mass spectrometry techniques help uncover these processes and find new antiviral targets.
Article
Nutrition & Dietetics
Sarah Brajkovic, Nils Rugen, Carlos Agius, Nicola Berner, Stephan Eckert, Amirhossein Sakhteman, Claus Schwechheimer, Bernhard Kuster
Summary: Plants are crucial for sustainable global food supply, but the understanding of crop proteomes is limited. The presence of secondary metabolites in crop plants has hindered proteomic analyses, requiring individually optimized protein extraction protocols. In this study, a universal protein extraction protocol combined with an automated SP3 protocol and optimized micro-LC-MS/MS conditions was developed for high-quality proteomic analysis of crop plants. The workflow was successfully applied to analyze the proteomes of mature tomato fruits, demonstrating its robustness and potential for large-scale projects mapping crop tissue proteomes.
Article
Chemistry, Analytical
Kyle A. Brown, Morgan K. Gugger, Zhen Yu, David Moreno, Song Jin, Ying Ge
Summary: Nonionic surfactants are commonly used reagents for cell lysis and protein extraction in structural biology. However, their presence often interferes with protein analysis by electrospray ionization-mass spectrometry (ESI-MS). This study introduces a cleavable surfactant, DSSM, which is compatible with ESI-MS analysis and enables top-down proteomics characterization. DSSM can replace DDM in proteomic experiments and structural biology studies.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Guorong Ma, Pengzheng Luo, Ruiqiang Xu, Rui Ma, Lei Qiu, Chenran Xu, Rang Yang, Yating Li, Zhihao Zhao, Ling Huang, Yanhui Yang, Pei Wang
Summary: This study used six biomimetic affinity chromatography (BiAC) resins to fractionate the cytoplasmic proteins of M. tuberculosis and identified a total of 1246 proteins. Compared with un-fractionated samples, BiAC fractionation improved the confidence and profile of M. tuberculosis cytoplasmic proteins.
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
(2023)
Article
Chemistry, Multidisciplinary
Jan Leipert, Philipp T. Kaulich, Max K. Steinbach, Britta Steer, Konrad Winkels, Christine Blurton, Matthias Leippe, Andreas Tholey
Summary: Researchers have developed a sample preparation method based on protein aggregation and acidic elution, allowing for sensitive protein identification analysis of single nematodes on a digital microfluidics device. Compared to in-tube sample preparation, this method increases proteoform identifications by 46%. Label-free quantification also reveals changes in proteoform abundance that cannot be distinguished by bottom-up proteomics. This workflow facilitates proteoform-focused analysis on limited availability samples.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Jake A. Melby, Kyle A. Brown, Zachery R. Gregorich, David S. Roberts, Emily A. Chapman, Lauren E. Ehlers, Zhan Gao, Eli J. Larson, Yutong Jin, Justin R. Lopez, Jared Hartung, Yanlong Zhu, Sean J. McIlwain, Daojing Wang, Wei Guo, Gary M. Diffee, Ying Ge
Summary: Single-cell proteomics is a powerful method to study cellular heterogeneity and functional networks. However, it faces challenges in analyzing proteoforms from genetic mutations, alternative splicing, and post-translational modifications. In this study, a sensitive top-down proteomics method was developed to analyze proteoforms from single muscle fibers. The study identified heterogeneity in large proteoforms and a relationship between sarcomeric proteoforms and muscle fiber types.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Chemistry, Analytical
Hanne Roberg-Larsen, Elsa Lundanes, Tuula A. Nyman, Frode S. Berven, Steven Ray Wilson
Summary: Single-cell analysis provides in-depth insights into diseases and diagnostics, with liquid chromatography playing a crucial role. The development of novel sample preparation techniques and improvements in mass spectrometry are enhancing the promise of single-cell analysis. However, technical challenges and the need for higher throughput and robustness may lead to the reinvention of alternative nano LC column formats.
ANALYTICA CHIMICA ACTA
(2021)
Article
Chemistry, Analytical
Kyle A. Brown, Morgan K. Gugger, Zhen Yu, David Moreno, Song Jin, Ying Ge
Summary: Nonionic surfactants are widely used in cell lysis for protein extraction, stabilization, and purification in structural biology. However, they often interfere with electrospray ionization-mass spectrometry (ESI-MS) analysis. In this study, a cleavable nonionic surfactant, n-decyl-disulfide-beta-D-maltoside (DSSM), was developed to overcome this limitation. DSSM is compatible with ESI-MS and reversed-phase liquid chromatography-MS analysis and allows for characterization of membrane proteins and endogenous proteins, making it a potential replacement for the commonly used surfactant DDM in proteomic experiments and structural biology studies.
ANALYTICAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Tanja Habeck, Edvaldo Vasconcelos Soares Maciel, Kevin Kretschmer, Frederik Lermyte
Summary: In recent years, top-down mass spectrometry has been widely used to study proteoforms, with the goal of improving sequence coverage. This study investigated the effects of two high-boiling solvents, DMSO and propylene carbonate, on the top-down fragmentation patterns of two different proteins. The results revealed reproducible differences in the fragmentation patterns in the presence of these additives, potentially due to the selective formation of different protonation site isomers. The presence of additives often led to higher sequence coverage, and combining datasets from different solution conditions further increased cleavage coverage.
Review
Biochemistry & Molecular Biology
Miguel Angel Galvan-Morales
Summary: Proteomics in respiratory allergic diseases offers a wide range of techniques and programs for diagnosis, treatment, and immunotherapy. The main focus is on blocking cell diapedesis, modifying and blocking paratopes and epitopes, and inhibiting FceRI high-affinity receptors to prevent IgE binding. However, there is still a need for identifying allergens and cross-reactions through structural and epitope identification. The use of proteomics remains crucial for diagnostics and controlled immunotherapy systems. It is proposed to utilize this vision for treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Chemistry, Analytical
Fanny C. Liu, Samuel R. Kirk, Kirsten A. Caldwell, Thais Pedrete, Florian Meier, Christian Bleiholder
Summary: Top-down proteomics is a challenging but direct approach to studying proteoforms. This study utilizes ion mobility spectrometry/mass spectrometry (IMS/MS) to separate top-down fragment ions and reveals that these ions exhibit multiple stable conformations influenced by their amino acid sequence. The study also suggests that the folding process of fragment ions can lead to kinetic trapping of intermediate states in ion mobility measurements.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Caraline Sepich-Poore, Zhong Zheng, Emily Schmitt, Kailong Wen, Zijie Scott Zhang, Xiao-Long Cui, Qing Dai, Allen C. Zhu, Linda Zhang, Arantxa Sanchez Castillo, Haiyan Tan, Junmin Peng, Xiaoxi Zhuang, Chuan He, Sigrid Nachtergaele
Summary: Ribosomal RNAs (rRNAs) carry various chemical modifications, including m6A, which play important roles in mRNA decoding. We identified the METTL5-TRMT112 methyltransferase complex as responsible for the m6A modification on human 18S rRNA. Loss of METTL5 disrupts gene expression and causes developmental defects in humans and mice.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Neurosciences
Erik C. B. Johnson, E. Kathleen Carter, Eric B. Dammer, Duc M. Duong, Ekaterina S. Gerasimov, Yue Liu, Jiaqi Liu, Ranjita Betarbet, Lingyan Ping, Luming Yin, Geidy E. Serrano, Thomas G. Beach, Junmin Peng, Philip L. De Jager, Vahram Haroutunian, Bin Zhang, Chris Gaiteri, David A. Bennett, Marla Gearing, Thomas S. Wingo, Aliza P. Wingo, James J. Lah, Allan I. Levey, Nicholas T. Seyfried
Summary: This study analyzed the proteomes of over 1,000 brain tissues and identified new protein co-expression modules associated with Alzheimer's disease. These modules were highly conserved across cohorts and brain regions and revealed a proteopathic nature of the disease. The study also found disease-associated modules unique to the proteome, which could serve as potential therapeutic targets and biomarkers for Alzheimer's disease.
NATURE NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Ling Li, Mingming Niu, Alyssa Erickson, Jie Luo, Kincaid Rowbotham, Kai Guo, He Huang, Yuxin Li, Yi Jiang, Junguk Hur, Chunyu Liu, Junmin Peng, Xusheng Wang
Summary: The integration of genomics and proteomics data (proteogenomics) shows promise in advancing our understanding of human disease. This study presents a pipeline called SMAP for verifying sample identity and ensuring data integrity in proteogenomics research. SMAP infers sample-specific protein-coding variants from mass spectrometry data and aligns proteomic samples with genomic samples using discriminant scores. The results demonstrate that SMAP is an effective tool for sample verification in large-scale MS-based proteogenomics studies.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Analytical
Xiaojun Sun, Huan Sun, Xian Han, Ping-Chung Chen, Yun Jiao, Zhiping Wu, Xue Zhang, Zhen Wang, Mingming Niu, Kaiwen Yu, Danting Liu, Kaushik Kumar Dey, Ariana Mancieri, Yingxue Fu, Ji-Hoon Cho, Yuxin Li, Suresh Poudel, Tess C. Branon, Alice Y. Ting, Junmin Peng
Summary: Proteome profiling is a powerful tool in biological and biomedical studies. In this study, a proximity labeling strategy using TurboID was presented for single-cell-type proteomics of mouse brain. This approach allows labeling of specific cell-type proteomes without the need for cell isolation and includes steps for protein purification and quantitative analysis.
ANALYTICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Seong Su Kang, Lanxia Meng, Xingyu Zhang, Zhiping Wu, Ariana Mancieri, Boer Xie, Xia Liu, David Weinshenker, Junmin Peng, Zhentao Zhang, Keqiang Ye
Summary: DOPEGAL, a metabolite of norepinephrine, covalently modifies tau and accelerates its aggregation and propagation, leading to cognitive deficits in Alzheimer's disease. The selective vulnerability of noradrenergic locus ceruleus (LC) neurons in AD may be explained by oxidation of norepinephrine via monoamine oxidase A (MAO-A) into DOPEGAL, which modifies tau and facilitates its aggregation, toxicity, and propagation.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Monicah N. Bwayi, Efren Garcia-Maldonado, Sergio C. Chai, Boer Xie, Shirish Chodankar, Andrew D. Huber, Jing Wu, Kavya Annu, William C. Wright, Hyeong-Min Lee, Jayaraman Seetharaman, Jingheng Wang, Cameron D. Buchman, Junmin Peng, Taosheng Chen
Summary: The interactions between nuclear receptors can fundamentally change our understanding of their biology. In this study, the molecular basis of crosstalk between the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) is revealed, demonstrating the formation of a novel heterodimer and mutual inhibition. These findings not only change the perceived functional relationship between PXR and CAR, but also provide new perspectives for elucidating their role and designing approaches to regulate them.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Oncology
Rosa Nguyen, Hong Wang, Ming Sun, Dong Geun Lee, Junmin Peng, Carol J. Thiele
Summary: This study suggests a potential therapeutic benefit in using selinexor and alisertib to synergistically increase p53-mediated cytotoxicity of high-risk neuroblastoma.
Article
Biochemistry & Molecular Biology
Huan Sun, Ka Yang, Xue Zhang, Yingxue Fu, Jay Yarbro, Zhiping Wu, Ping-Chung Chen, Taosheng Chen, Junmin Peng
Summary: Chemoproteomics is a crucial platform for studying the mode of action of compounds. This study presents a pooling strategy to enhance throughput and applies it to a drug library. The findings demonstrate that pooling chemoproteomics screening is an efficient method for dissecting the molecular targets of compound libraries.
Article
Biochemistry & Molecular Biology
Giovanni Quarato, Fabien Llambi, Cliff S. Guy, Jaeki Min, Marisa Actis, Huan Sun, Shilpa Narina, Shondra M. Pruett-Miller, Junmin Peng, Zoran Rankovic, Douglas R. Green
Summary: The imbalance of intracellular Ca2+ and mitochondrial Ca2+ overload can lead to mitochondrial inner membrane permeabilization and cell death, which is distinct from Bcl-2 family-regulated mitochondrial outer membrane permeabilization. Cyclosporin A can prevent cell death by inhibiting Ca2+ release from endoplasmic reticulum stores.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Neurosciences
Chia-Chen Liu, Jing Zhao, Yuan Fu, Yasuteru Inoue, Yingxue Ren, Yuanxin Chen, Sydney V. Doss, Francis Shue, Suren Jeevaratnam, Ligia Bastea, Na Wang, Yuka A. Martens, Wenhui Qiao, Minghui Wang, Na Zhao, Lin Jia, Yu Yamazaki, Akari Yamazaki, Cassandra L. Rosenberg, Zhen Wang, Dehui Kong, Zonghua Li, Lindsey A. Kuchenbecker, Zachary A. Trottier, Lindsey Felton, Justin Rogers, Zachary S. Quicksall, Cynthia Linares, Joshua Knight, Yixing Chen, Aishe Kurti, Takahisa Kanekiyo, John D. Fryer, Yan W. Asmann, Peter Storz, Xusheng Wang, Junmin Peng, Bin Zhang, Betty Y. S. Kim, Guojun Bu
Summary: Peripheral apoE4 has detrimental effects on cognition and amyloid pathology by compromising vascular integrity and function. It impairs synaptic plasticity and cognition and influences functional pathways such as cell adhesion, lipoprotein metabolism, and complement activation. ApoE3 plasma from young mice improves cognition and reduces vessel-associated gliosis, while liver-expressed apoE4 exacerbates brain amyloid pathology.
NATURE NEUROSCIENCE
(2022)
Article
Biochemical Research Methods
Huan Sun, Suresh Poudel, David Vanderwall, Dong Geun Lee, Yuxin Li, Junmin Peng
Summary: Tandem mass tag (TMT) mass spectrometry is a popular labeling strategy for protein profiling. In this study, a 29-plex TMT method was developed and validated using pooled samples, demonstrating its ability to correct for noise and restore expected ratio values.
Article
Cell Biology
Shivendra Singh, Ahmed Abu-Zaid, Hongjian Jin, Jie Fang, Qiong Wu, Tingting Wang, Helin Feng, Waise Quarni, Ying Shao, Lily Maxham, Alireza Abdolvahabi, Mi-Kyung Yun, Sivaraja Vaithiyalingam, Haiyan Tan, John Bowling, Victoria Honnell, Brandon Young, Yian Guo, Richa Bajpai, Shondra M. Pruett-Miller, Gerard C. Grosveld, Mark Hatley, Beisi Xu, Yiping Fan, Gang Wu, Eleanor Y. Chen, Taosheng Chen, Peter W. Lewis, Zoran Rankovic, Yimei Li, Andrew J. Murphy, John Easton, Junmin Peng, Xiang Chen, Ruoning Wang, Stephen W. White, Andrew M. Davidoff, Jun Yang
Summary: This study identifies KDM4B as a therapeutic vulnerability for PAX3-FOXO1(+) RMS. Inhibition of KDM4B delays tumor growth and suppresses the expression of core oncogenic transcription factors, causing epigenetic alterations of PAX3-FOXO1-governed superenhancers.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Chemistry, Medicinal
Andrew D. Huber, Yongtao Li, Wenwei Lin, Annalise N. Galbraith, Ashutosh Mishra, Shaina N. Porter, Jing Wu, Rebecca R. Florke Gee, Wei Zhuang, Shondra M. Pruett-Miller, Junmin Peng, Taosheng Chen
Summary: This study describes the discovery of a molecule, SJPYT-195, which can reduce the protein level of PXR by acting as a molecular glue degrader of GSPT1, a translation termination factor. The findings provide insights into the chemical determinants of drug-induced GSPT1 degradation and also present assays and cell models for the discovery of PXR degraders.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
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.
Meeting Abstract
Biochemistry & Molecular Biology
Junmin Peng
JOURNAL OF NEUROCHEMISTRY
(2022)