Editorial Material
Biochemistry & Molecular Biology
Filip Nemcko, Alexander Stark
Summary: In this issue of Molecular Cell, researchers present a proteome-scale functional screen to systematically uncover human proteins that can activate transcription.
Article
Biochemistry & Molecular Biology
Caroline Benz, Muhammad Ali, Izabella Krystkowiak, Leandro Simonetti, Ahmed Sayadi, Filip Mihalic, Johanna Kliche, Eva Andersson, Per Jemth, Norman E. Davey, Ylva Ivarsson
Summary: Specific protein-protein interactions are crucial for cell physiology, but many interactions are yet to be discovered. This study introduces an optimized peptide-phage display library that allows for the screening of numerous peptides in a single binding assay, aiding the discovery of SLiM-based interactions.
MOLECULAR SYSTEMS BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Dae-Kyum Kim, Benjamin Weller, Chung-Wen Lin, Dayag Sheykhkarimli, Jennifer J. Knapp, Guillaume Dugied, Andreas Zanzoni, Carles Pons, Marie J. Tofaute, Sibusiso B. Maseko, Kerstin Spirohn, Florent Laval, Luke Lambourne, Nishka Kishore, Ashyad Rayhan, Mayra Sauer, Veronika Young, Hridi Halder, Nora Marin-de la Rosa, Oxana Pogoutse, Alexandra Strobel, Patrick Schwehn, Roujia Li, Simin T. Rothballer, Melina Altmann, Patricia Cassonnet, Atina G. Cote, Lena Elorduy Vergara, Isaiah Hazelwood, Betty B. Liu, Maria Nguyen, Ramakrishnan Pandiarajan, Bushra Dohai, Patricia A. Rodriguez Coloma, Juline Poirson, Paolo Giuliana, Luc Willems, Mikko Taipale, Yves Jacob, Tong Hao, David E. Hill, Christine Brun, Jean-Claude Twizere, Daniel Krappmann, Matthias Heinig, Claudia Falter, Patrick Aloy, Caroline Demeret, Marc Vidal, Michael A. Calderwood, Frederick P. Roth, Pascal Falter-Braun
Summary: A study mapping the contactome between SARS-CoV-2 and human host proteins uncovers an inhibitor of viral replication and connects it to COVID-19 severity and human genetic architecture, providing important insights for therapy design and drug development.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Brandon M. Gassaway, Jiaming Li, Ramin Rad, Julian Mintseris, Kyle Mohler, Tyler Levy, Mike Aguiar, Sean A. Beausoleil, Joao A. Paulo, Jesse Rinehart, Edward L. Huttlin, Steven P. Gygi
Summary: Iterative Synthetically Phosphorylated Isomers (iSPI) is a proteome-scale library of human-derived phosphoserine-containing phosphopeptides with precisely known positions of phosphorylation. It serves as a valuable resource for optimization, standardization, and benchmarking in phosphoproteomics workflows, and addresses the lack of inexpensive and diverse phosphopeptides with ground-truth phosphorylation positions.
Article
Biochemistry & Molecular Biology
Jiaming Li, Zhenying Cai, Laura Pontano Vaites, Ning Shen, Dylan C. Mitchell, Edward L. Huttlin, Joao A. Paulo, Brian L. Harry, Steven P. Gygi
Summary: By combining cycloheximide chase assays with advanced quantitative proteomics, this study mapped short-lived proteins under translational inhibition in four human cell lines. Short-lived proteins are less abundant, evolutionarily younger, and less thermally stable compared to other proteins, with 103 proteins showing different stabilities among cell lines. Truncated forms of certain proteins in U2OS and HCT116 cells were also identified, indicating lower stability than full-length counterparts. This research provides a large-scale resource for understanding human short-lived proteins and their potential for therapeutic interventions.
Article
Biochemical Research Methods
Nirjara Singhvi, Priya Singh, Om Prakash, Vipin Gupta, Sukanya Lal, Andreas Bechthold, Yogendra Singh, Rakesh Kumar Singh, Rup Lal
Summary: This study revealed the mechanisms of rifamycin biosynthesis in Amycolatopsis mediterranei through genetic engineering, identifying regulatory hubs crucial for improving strain production of analogs/drugs. This contributes significantly to the knowledge in the field and can be useful for eradicating TB caused by rifampicin-resistant strains.
JOURNAL OF PROTEOMICS
(2021)
Review
Biochemistry & Molecular Biology
Clinton Yu, Lan Huang
Summary: Understanding protein-protein interaction networks and their structural features is crucial for unraveling fundamental biology and linking cell phenotypes to human pathologies. Cross-linking mass spectrometry (XL-MS), along with high-resolution structural tools, has significantly contributed to elucidating the architectures of large protein assemblies and advancing structural systems biology.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Edward L. Huttlin, Raphael J. Bruckner, Jose Navarrete-Perea, Joe R. Cannon, Kurt Baltier, Fana Gebreab, Melanie P. Gygi, Alexandra Thornock, Gabriela Zarraga, Stanley Tam, John Szpyt, Brandon M. Gassaway, Alexandra Panov, Hannah Parzen, Sipei Fu, Arvene Golbazi, Eila Maenpaa, Keegan Stricker, Sanjukta Guha Thakurta, Tian Zhang, Ramin Rad, Joshua Pan, David P. Nusinow, Joao A. Paulo, Devin K. Schweppe, Laura Pontano Vaites, J. Wade Harper, Steven P. Gygi
Summary: This study explores thousands of interactions between proteins, creating two essential cell-line specific interaction networks that help researchers understand the principles of proteome organization and unknown protein characteristics. Comparing different cell lines revealed extensive customization, linking core complexes with essential proteins and rewiring subnetworks to produce each cell's phenotype.
Article
Multidisciplinary Sciences
Adam C. O'Neill, Fatma Uzbas, Giulia Antognolli, Florencia Merino, Kalina Draganova, Alex Jaeck, Sirui Zhang, Giorgia Pedini, Julia P. Schessner, Kimberly Cramer, Aloys Schepers, Fabian Metzger, Miriam Esgleas, Pawel Smialowski, Renzo Guerrini, Sven Falk, Regina Feederle, Saskia Freytag, Zefeng Wang, Melanie Bahlo, Ralf Jungmann, Claudia Bagni, Georg H. H. Borner, Stephen P. Robertson, Stefanie M. Hauck, Magdalena Goetz
Summary: The centrosome serves as an anchor for the cytoskeleton and plays a crucial role in cell division, migration, and cilia formation. By using spatial proteomics, researchers have uncovered protein interaction networks specific to the centrosome in human induced pluripotent stem cell-derived neural stem cells and neurons. These cell type-specific centrosome interactomes explain how genetic variants in widespread proteins can lead to brain-specific phenotypes.
Article
Biochemical Research Methods
Russell B. Davidson, Mark Coletti, Mu Gao, Bryan Piatkowski, Avinash Sreedasyam, Farhan Quadir, David J. Weston, Jeremy Schmutz, Jianlin Cheng, Jeffrey Skolnick, Jerry M. Parks, Ada Sedova
Summary: This study utilizes AlphaFold to predict the structural proteome of Sphagnum divinum, and provides structure alignment and enzyme classification, filling the gaps in the field of protein structure for Sphagnum species.
Article
Microbiology
Florian Stieglitz, Ralf Gerhard, Andreas Pich
Summary: Clostridioides difficile is a major cause of nosocomial infections worldwide, mainly due to toxin A and toxin B. Hypervirulent strains producing CDT toxin are associated with higher mortality rates. The study revealed that treatment with CDTa and CDTb led to changes in phosphorylation levels of around 1100 phosphosites, indicating potential involvement of CSNK2A1 as an effector kinase for CDTa.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Cell Biology
Kai-Wen Cheng, Shan Li, Feng Wang, Nallely M. Ruiz-Lopez, Nadia Houerbi, Tsui-Fen Chou
Summary: Research shows that the essential host protein p97 plays a crucial role in supporting human coronavirus replication, with inhibition of p97 showing antiviral activity at early stages of the virus life cycle and protecting cells from virus-induced damage. Additionally, p97 inhibition inhibits viral production in infected cells, indicating p97 as a potential therapeutic target for treating coronavirus infections.
Article
Oncology
Zivojin Jevtic, Vittoria Matafora, Francesca Casagrande, Fabio Santoro, Saverio Minucci, Massimilliano Garre, Milad Rasouli, Olaf Heidenreich, Giovanna Musco, Juerg Schwaller, Angela Bachi
Summary: The study reveals that the NUP98-NSD1 fusion protein plays a transformative role in hematopoietic cells through its interaction and colocalization with SMARCA5. The formation of NUP98-NSD1 nuclear condensates is not enough to maintain the transformed phenotype, suggesting that selectively targeting condensate constituents could be a new therapeutic strategy for NUP98-NSD1 driven AML.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Immunology
Daisy H. Luff, Katarzyna Wojdyla, David Oxley, Tamara Chessa, Kevin Hudson, Phillip T. Hawkins, Len R. Stephens, Simon T. Barry, Klaus Okkenhaug
Summary: In T cells, PI3K delta rapidly interacts with multiple adaptor proteins, including GAB family proteins, ICOS, and TRIM, and pre-forms complexes to facilitate its activation at the plasma membrane. There is a large protein network in CD4(+) T cells that regulates the recruitment and activation of PI3K delta. The PI3K delta interactome undergoes remodeling at different stages of T cell differentiation.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Gou Takahashi, Daiki Kondo, Minato Maeda, Yuji Morishita, Yuichiro Miyaoka
Summary: This study utilized the Single Particle isolation System to analyze genome editing outcomes in individual human cultured cells, revealing a binary nature of genome editing induction and providing a new strategy for analyzing genome editing outcomes in single cells.
Article
Chemistry, Analytical
Marthe M. Vandeputte, Alex J. Krotulski, Fabian Hulpia, Serge Van Calenbergh, Christophe P. Stove
Summary: Profiling the illicit fentanyl supply is crucial for surveillance and intelligence purposes. This report focuses on the identification of a previously unknown compound, phenethyl-4-ANPP, and its potential role in fentanyl manufacturing routes.
JOURNAL OF ANALYTICAL TOXICOLOGY
(2022)
Review
Pharmacology & Pharmacy
Dorien Clarisse, Lisa Deng, Karolien de Bosscher, Achim Lother
Summary: Mineralocorticoid receptor antagonists are effective therapies for cardiovascular and renal diseases, but their widespread clinical use is limited by the risk of hyperkalaemia. New strategies are needed to selectively target the harmful effects of the mineralocorticoid receptor while preserving its physiological function.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Charlotte Courtens, Frits van Charante, Thibaut Quennesson, Martijn Risseeuw, Paul Cos, Guy Caljon, Tom Coenye, Serge Van Calenbergh
Summary: Fosmidomycin is a natural antibiotic that inhibits IspC. It is essential in bacterial and apicomplexan parasite biosynthesis pathways. However, its high polarity and inability to penetrate bacterial cell walls limit its effectiveness. By temporarily masking the phosphonate moiety as a prodrug, the researchers were able to discover derivatives with improved activity against Plasmodium and A. baumanii.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Muhammad Rishfi, Simon Krols, Fien Martens, Sarah-Lee Bekaert, Ellen Sanders, Aline Eggermont, Fanny De Vloed, Joshua Robert Goulding, Martijn Risseeuw, Jan Molenaar, Bram De Wilde, Serge Van Calenbergh, Kaat Durinck
Summary: We conducted a structure-activity relationship (SAR) study of MK-5108-derived PROTACs against AURKA in neuroblastoma. SK2188 showed the most potent AURKA degradation and excellent binding and degradation selectivity. It induced MYCN degradation, replication stress/DNA damage, and apoptosis in neuroblastoma cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemical Research Methods
Elke Debrie, Milan Malfait, Ralf Gabriels, Arthur Declerq, Adriaan Sticker, Lennart Martens, Lieven Clement
Summary: Reliable peptide identification is crucial in MS-based proteomics, and the TDA method is widely used for estimating the FDR. However, the assumptions of TDA are often not verified in practice, which can result in poor FDR control and negatively impact downstream data analysis. To address this issue, the TargetDecoy package is introduced, providing necessary functionality to assess the quality and assumptions of TDA for a given set of PSMs.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Ralf Gabriels, Arthur Declercq, Robbin Bouwmeester, Sven Degroeve, Lennart Martens
Summary: There are various output file formats from proteomics search engines, but the lack of standardized formats makes it difficult to process peptide-spectrum matches (PSMs) and PSM files downstream. This article presents psm_utils, a Python package that can handle various PSM file formats and provides a unified and user-friendly interface. It includes a Python API, a command line interface, and a web application for interconverting PSM files and retrieving basic PSM statistics.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Marzuq A. Ungogo, Mustafa M. Aldfer, Manal J. Natto, Hainan Zhuang, Robyn Chisholm, Katy Walsh, MarieClaire McGee, Kayhan Ilbeigi, Jamal Ibrahim Asseri, Richard J. S. Burchmore, Guy Caljon, Serge Van Calenbergh, Harry P. De Koning
Summary: African Animal Trypanosomiasis (AAT) is a fatal livestock disease in Sub-Saharan Africa caused by Trypanosoma brucei brucei, T. vivax, and T. congolense. Limited treatment options and resistance threaten the control of this disease. In this study, the adenosine transporters of T. vivax (TvxNT3) and T. congolense (TcoAT1/NT10) were characterized and their functional expression was demonstrated. The findings suggest that nucleoside chemotherapy for AAT is viable based on the similarities in nucleoside sensitivity among different parasite species and the interactions with nucleoside transporters.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemical Research Methods
Benjamin A. Neely, Viktoria Dorfer, Lennart Martens, Isabell Bludau, Robbin Bouwmeester, Sven Degroeve, Eric W. Deutsch, Siegfried Gessulat, Lukas Kaell, Pawel Palczynski, Samuel H. Payne, Tobias Greisager Rehfeldt, Tobias Schmidt, Veit Schwaemmle, Julian Uszkoreit, Juan Antonio Vizcaino, Mathias Wilhelm, Magnus Palmblad
Summary: In recent years, machine learning has made significant progress in modeling mass spectrometry data for proteomics analysis. A workshop was conducted to evaluate and explore machine learning applications in multidimensional mass spectrometry-based proteomics analysis. The workshop helped identify knowledge gaps, define needs, and discuss the possibilities, challenges, and future opportunities. The summary of the discussions conveys excitement about the potential of machine learning in proteomics and aims to inspire future research.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Tine Claeys, Maxime Menu, Robbin Bouwmeester, Kris Gevaert, Lennart Martens
Summary: Using data from 183 public human data sets, a machine learning model was trained to identify tissue and cell-type specific protein patterns. The model achieved high accuracy in predicting tissues (98%) and cell types (99%) based on protein abundance. The results provide valuable insights into tissue-specific proteins and can be applied to various downstream applications.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Biochemical Research Methods
Pieter Verschaffelt, Alessandro Tanca, Marcello Abbondio, Tim van den Bossche, Tibo Vande Moortele, Peter Dawyndt, Lennart Martens, Bart Mesuere
Summary: Unipept Desktop 2.0 is the latest version of the Unipept Desktop tool, which now supports the analysis of metaproteogenomics datasets. It allows for the automatic construction of targeted protein reference databases for improved taxonomic and functional resolution. By limiting the proteins in the database, (meta)proteogenomic analyses can also be performed with better control and privacy. A case study using human gut metaproteome dataset and matched 16S rRNA gene sequencing data is presented as a proof of concept.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Tine Claeys, Tim van den Bossche, Yasset Perez-Riverol, Kris Gevaert, Juan Antonio Vizcaino, Lennart Martens
Summary: Public proteomics data often lack essential metadata, but lesSDRF provides a tool to simplify the process of metadata annotation and ensure that the data has lasting impact beyond its initial publication.
NATURE COMMUNICATIONS
(2023)
Article
Biochemical Research Methods
Ralf Gabriels, Arthur Declercq, Robbin Bouwmeester, Sven Degroeve, Lennart Martens
Summary: This study introduces a Python package called psm_utils, which can read and write various proteomics search engine output file formats and handle peptide-spectrum matches (PSMs) and PSM lists in a unified data structure. The package includes a Python API and command line interface, as well as a user-friendly web application for converting PSM files and retrieving basic PSM statistics.
JOURNAL OF PROTEOME RESEARCH
(2023)
Meeting Abstract
Clinical Neurology
R. Raedt, E. Craey, J. Spanoghe, L. E. Larsen, K. Vonck, E. Carrette, J. Delbeke, M. Sprengers, S. Van Calenbergh, W. J. Wadman, P. Boon
Article
Chemistry, Multidisciplinary
Silke Geurs, Dorien Clarisse, Freya Baele, Jorick Franceus, Tom Desmet, Karolien De Bosscher, Matthias D'hooghe
Summary: In this study, a set of HDAC6-selective inhibitors with low side effects and significant inhibitory activity in the nanomolar range were successfully synthesized using a lean inhibitor strategy.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Jacobus C. Buurstede, Susana N. Paul, Karolien De Bosscher, Onno C. Meijer, Jan Kroon
Summary: Glucocorticoids exert their effects by activating the glucocorticoid receptor (GR) throughout the body. This study investigated the interaction between glucocorticoids and androgen signaling in the liver transcriptome. The results showed that a substantial proportion of the hepatic transcriptome is androgen-dependent after chronic exposure, while the effects of glucocorticoids are largely androgen-independent after acute exposure. The study suggests that prolonged glucocorticoid exposure may upregulate androgen receptor expression, leading to androgen dependence not driven by direct interactions between the androgen receptor and glucocorticoid receptor.