Article
Biochemistry & Molecular Biology
Francesca Sacco, Matteo Tarchi, Giarita Ferraro, Antonello Merlino, Giorgio Facchetti, Isabella Rimoldi, Luigi Messori, Lara Massai
Summary: The study investigated the reactions of three novel platinum(II) complexes with model proteins through ESI MS analysis, revealing diverse reactivity patterns depending on the nature of the Pt complex and interacting proteins. The formation of protein-bound Pt fragments was identified, and crystal structures were used to determine the exact location of Pt binding sites, contributing to understanding the potential mechanisms of action of these innovative anticancer Pt complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Stefano Barbera, Luisa Raucci, Giusy Tassone, Laura Tinti, Filippo Prischi, Annalisa Santucci, Maurizio Mongiat, Gian Marco Tosi, Federico Galvagni, Anna Dimberg, Cecilia Pozzi, Maurizio Orlandini
Summary: Blocking the signaling activated by the plasma membrane receptor CD93 has been shown to be useful in antiangiogenic treatment and oncotherapy. CD93 structurally exists as a dimer in endothelial cells and its oligomeric form is important for binding to its ligand Multimerin-2. Crystallographic analysis reveals the role of the C-type lectin-like and sushi-like domains in achieving a functional binding state, which provides valuable information for the development of drugs targeting CD93 in neovascular pathologies.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Biochemical Research Methods
Smarajit Mondal, Muthukumar Ramanathan, Weili Miao, Robin M. Meyers, Deepti Rao, Vanessa Lopez-Pajares, Zurab Siprashvili, David L. Reynolds, Douglas F. Porter, Ian Ferguson, Poornima Neela, Yang Zhao, Lindsey M. Meservey, Margaret Guo, Yen-Yu Yang, Lin Li, Yinsheng Wang, Paul A. Khavari
Summary: DNA-protein interactions play a crucial role in gene regulation and can be affected by DNA variants associated with polygenic diseases. A new method called PROBER has been developed to rapidly identify and quantify proteins associated with specific DNA sequences in living cells. PROBER utilizes high-copy episomes and proximity proteomics to accurately identify transcription factors and gene regulators associated with target DNA sequences and single-nucleotide variants. The method has been used to study the impact of cancer hotspot mutations on regulator associations.
Article
Cell Biology
Lekha Jain, Mark H. Vickers, Bincy Jacob, Martin J. Middleditch, Daria A. Chudakova, Austen R. D. Ganley, Justin M. O'Sullivan, Jo K. Perry
Summary: Growth hormone (GH) activates downstream signalling by binding to its cell-surface receptor, the GH receptor (GHR). However, nuclear localization of GHR has been observed and linked to increased cancer cell proliferation. In this study, the authors investigated the functional implications of GHR nuclear translocation in two cancer cell lines and identified potential interactions with chromatin factors. The findings suggest that GHR nuclear translocation might mediate GH actions by influencing downstream transcriptional programs.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Article
Medicine, Legal
Yao-Te Yen, Mei-Chun Liu, Chun-Yi Liu, Cheng-Han Hung, Pei-Lin Chen, San-Chong Chyueh
Summary: Single-crystal X-ray crystallography played a crucial role in identifying the structure of N-(2,6-dimethyl-phenyl)-1-phenethylpiperidine-2-carboxamide (NDMPPPC), a new psychoactive substance with pharmacological effects similar to cocaine, ketamine, and morphine. This demonstrates the potential of single-crystal X-ray diffraction for structural determination in complex structures of new drugs or unknown samples.
FORENSIC SCIENCE INTERNATIONAL
(2021)
Article
Chemistry, Analytical
Jin Tang, Wenxin Zhao, Nathan G. Hendricks, Linlin Zhao
Summary: The study developed a method that allows for the identification of cross-linking amino acid residues in DNA-protein cross-links at single amino acid resolution by leveraging the alkaline lability of ribonucleotides. The method improved ionization, reduced the database search space, and facilitated the identification of cross-linking residues in peptides.
ANALYTICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Tiziano Marzo, Giarita Ferraro, Lorena Maria Cucci, Alessandro Pratesi, Orjan Hansson, Cristina Satriano, Antonello Merlino, Diego La Mendola
Summary: The study shows that the anti-cancer drug oxaliplatin efficiently binds angiogenin, inhibiting its promoting effects on cell proliferation and migration. This suggests angiogenin as a potential target of oxaliplatin, indicating a new mechanism for the anti-neoplastic activity of this platinum drug and opening avenues for novel approaches in combined anti-cancer anti-angiogenic therapy.
JOURNAL OF INORGANIC BIOCHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Marta L. Mendes, Gunnar Dittmar
Summary: The structure of the 26S proteasome, essential for protein degradation and maintaining cell homeostasis, has been successfully determined using cryo-electron microscopy, revealing at least seven different conformational states. The application of cross-linking mass spectrometry in integrative structural biology studies promises to answer more unanswered questions.
Article
Multidisciplinary Sciences
Adam G. Kreutzer, Gretchen Guaglianone, Stan Yoo, Chelsea Marie T. Parrocha, Sarah M. Ruttenberg, Ryan J. Malonis, Karen Tong, Yu-Fu Lin, Jennifer T. Nguyen, William J. Howitz, Michelle N. Diab, Imane L. Hamza, Jonathan R. Lai, Vicki H. Wysocki, James S. Nowick
Summary: The assembly of A(3 peptide is closely associated with Alzheimer's disease. Two covalently stabilized isomorphic trimers derived from A(3) were compared in terms of their structure, biophysical and biological characteristics. The trimers exhibited different assembly and biological properties, with one forming small soluble oligomers and the other forming large insoluble aggregates. The two trimers also had different effects on the aggregation, toxicity, and cellular interaction of full-length A(3). These findings provide insights into the differences among A(3 oligomers.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medical Laboratory Technology
Jason K. Y. Lee, Kendall Cradic, Ravinder J. Singh, JoAnna Jones, Jieli Li
Summary: This study compared the measurement of IGF-1 on four different platforms and found significant variations between them. These variations should be considered when managing patients with pituitary disorders.
CLINICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Oliver J. Hale, Helen J. Cooper
Summary: This study demonstrates a mass spectrometry analysis method for the direct analysis of intact oligomeric membrane proteins from tissue. By characterizing protein assembly directly from sheep eye lens sections without sample pre-treatment, our approach allows for simultaneous analysis of soluble protein assemblies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Chemistry, Multidisciplinary
Muhammad A. Zenaidee, Joseph A. Loo
Summary: Extending mass spectrometry measurements of biomolecules into the megadalton regime is challenging. However, using single ion-charge detection Orbitrap mass spectrometry, a mass accuracy of 0.001% has been demonstrated for protein particles larger than 9 MDa.
Article
Biochemistry & Molecular Biology
Di Wang, Valeriia Kuzyk, Katarina Madunic, Tao Zhang, Oleg A. Mayboroda, Manfred Wuhrer, Guinevere S. M. Lageveen-Kammeijer
Summary: Colorectal cancer (CRC) is a common and deadly type of cancer. Studying the N-glycosylation of CRC cell lines can help identify potential therapeutic and diagnostic targets. The study found a diverse range of N-glycans among the examined CRC cell lines and discovered similarities between different platforms used for analysis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cardiac & Cardiovascular Systems
Punashi Dutta, Karthik M. Kodigepalli, Stephanie LaHaye, J. Will Thompson, Sarah Rains, Casey Nagel, Kaitlyn Thatcher, Robert B. Hinton, Joy Lincoln
Summary: The study demonstrates the potential benefits of repurposing the selective XPO1 inhibitor drug KPT-330 for the treatment of CAVD. By inhibiting specific transcription factors and regulating the Wnt signaling pathway, KPT-330 shows promise in preventing and treating CAVD.
CIRCULATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Ozgur Yurekten, Thomas Payne, Noemi Tejera, Felix Xavier Amaladoss, Callum Martin, Mark Williams, Claire O'Donovan
Summary: MetaboLights is a global database for metabolomics studies that contains raw experimental data and associated metadata. It includes metabolite structures, reference spectra, and biological roles. This article discusses the growth and diversity of submissions to the database and highlights the development of MetaboLights Labs, a standardized workflow platform. The reuse of data by the community is also emphasized.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Abraham O. Oluwole, Robin A. Corey, Chelsea M. Brown, Victor M. Hernandez-Rocamora, Phillip J. Stansfeld, Waldemar Vollmer, Jani R. Bolla, Carol Robinson
Summary: The use of native mass spectrometry revealed the effects of lipid substrates on PG membrane enzymes and demonstrated that the passage of substrates and products in the pathway is controlled by their relative binding affinities.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Herman K. H. Fung, Shelley Grimes, Alexis Huet, Robert L. Duda, Maria Chechik, Joseph Gault, Carol Robinson, Roger W. Hendrix, Paul J. Jardine, James F. Conway, Christoph G. Baumann, Alfred A. Antson
Summary: Many cellular processes rely on substrate rotation or translocation by a multi-subunit, ring-type NTPase. Researchers have reconstituted a cos packaging system and provided a detailed description of its biochemical and structural properties, revealing similarities and differences in its mechanism and regulation.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Sean A. Cullum, Dmitry B. Veprintsev, Stephen J. Hill
Summary: This study analysed the kinetic phases of cAMP responses to beta(2)-adrenoceptor agonists in HEK293 cells expressing low levels of endogenous beta(2)-adrenoceptor. It was found that partial agonists had reduced relative IRmax values compared to isoprenaline. Preincubation with beta(2)-adrenoceptor antagonists led to a decrease in the peak response and exacerbated the effect on IRmax values. These findings provide insights into the hemi-equilibria in low receptor reserve systems with agonist-antagonist interactions.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Di Wu, Manman Guo, Carol V. Robinson
Summary: Understanding the impact of genetic variations and post-translational modifications on protein interactions is made possible by using native mass spectrometry (MS). In this study, we characterized the proteoforms of plasma serine protease inhibitors and found that different fucosylation linkages have opposing effects on protein interactions.
Article
Chemistry, Multidisciplinary
Tarick J. El-Baba, Corinne A. Lutomski, Sean A. Burnap, Jani R. Bolla, Lindsay A. Baker, Andrew J. Baldwin, Weston B. Struwe, Carol V. Robinson
Summary: In this study, the impact of glycans on mediating ACE2 dimerization and interactions with Spike was investigated. The researchers found that glycans play a regulatory role in ACE2 dimerization and that positive cooperativity drives ACE2 to complex with multiple Spike trimers. These findings are important for developing strategies to neutralize the virus.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Correction
Biochemistry & Molecular Biology
Rei Matsuoka, Roman Fudim, Sukkyeong Jung, Chenou Zhang, Andre Bazzone, Yurie Chatzikyriakidou, Carol V. Robinson, Norimichi Nomura, So Iwata, Michael Landreh, Laura Orellana, Oliver Beckstein, David Drew
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2023)
Review
Pharmacology & Pharmacy
Hsin-Yung Yen, Ali Jazayeri, Carol Robinson
Summary: GPCRs are important drug targets due to their involvement in physiological processes. Mass spectrometry techniques, such as HDX-MS and native-MS, provide opportunities to investigate GPCR pharmacology and discover new drugs. This review highlights the potential of MS techniques for in-depth investigations of GPCR biology.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Benjamin J. Hardy, Alvaro Martin Hermosilla, Dinesh K. Chinthapalli, Carol V. Robinson, J. L. Ross Anderson, Paul Curnow
Summary: In this study, a minimal diheme membrane cytochrome was computationally designed and produced in live bacteria. The synthetic construct mimics a four-helix bundle found in respiratory complexes and has no sequence homology to natural polypeptides. This artificial membrane metalloprotein has the potential to function as an electron transfer module in both synthetic protocells and living systems.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Gabriela Dias Noske, Yun Song, Rafaela Sachetto Fernandes, Rod Chalk, Haitem Elmassoudi, Lizbe Koekemoer, C. David J. Owen, Tarick V. El-Baba, Carol Robinson, Glaucius Oliva, Andre Schutzer Godoy
Summary: The main protease of SARS-CoV-2, M-pro, is responsible for cleaving the viral polyprotein and is crucial for enzyme dimerization and activity. N-terminal cleavage is not critical for dimerization, and different types of inhibitors can affect the oligomeric states. This study provides insights into the maturation process of M-pro and how it can be targeted by inhibitors.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Xiaomin Ni, Andreas C. Joerger, Apirat Chaikuad, Stefan Knapp
Summary: FUBP-interacting repressor (FIR) is a suppressor of the proto-oncogene MYC's transcription, by binding to the far upstream element (FUSE) of the MYC promoter. Competition with FUSE-binding protein 1 (FUBP1) is a crucial mechanism for MYC transcriptional regulation.
Article
Biochemical Research Methods
Maeva M. Pichon, Dawid Drelinkiewicz, David Lozano, Ruxandra Moraru, Laura J. Hayward, Megan Jones, Michael A. Mccoy, Samuel Allstrum-Graves, Dimitrios-Ilias Balourdas, Andreas C. Joerger, Richard J. Whitby, Stephen M. Goldup, Neil Wells, Graham J. Langley, Julie M. Herniman, Matthias G. J. Baud
Summary: Protein arylation using 2-sulfonylpyrimidines as covalent warheads for selective and metal-free cysteine S-arylation was evaluated. The reaction resulted in stable S-heteroarylated adducts at neutral pH. Fine-tuning of the heterocyclic core and exocyclic leaving group allowed predictable reactivity, covering >9 orders of magnitude. This study provides a comprehensive structure-reactivity relationship on heteroaryl sulfones and highlights 2-sulfonylpyrimidine as a synthetically tractable and protein compatible covalent motif for targeting reactive cysteines.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Biochemical Research Methods
Kenneth R. R. Durbin, Matthew T. T. Robey, Lilien N. N. Voong, Ryan T. T. Fellers, Corinne A. A. Lutomski, Tarick J. J. El-Baba, Carol V. V. Robinson, Neil L. L. Kelleher
Summary: Native mass spectrometry has become an important technique for determining the composition of protein complexes. However, there is a lack of software tools for comprehensive analysis of native mass spectrometry data. In this study, we introduce ProSight Native as an informatics platform that can determine the complete composition of protein complexes. We demonstrated its features by successfully determining the composition of a homotetrameric membrane complex and a heterodimer complex with associated ligands.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Miroslav Kosar, David A. Sykes, Alexander E. G. Viray, Rosa Maria Vitale, Roman C. Sarott, Rudolf L. Ganzoni, David Onion, Janelle M. Tobias, Philipp Leippe, Christoph Ullmer, Elisabeth A. Zirwes, Wolfgang Guba, Uwe Grether, James A. Frank, Dmitry B. Veprintsev, Erick M. Carreira
Summary: The study presents a novel ligand-directed covalent labeling strategy for visualizing and studying CB2R, a promising target for the treatment of neuroinflammatory disorders. The selective covalent labeling of CB2R was achieved using fluorogenic probes, and the probes were successfully applied to visualize CB2R in live cells.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Multidisciplinary Sciences
Hongmiao Hu, Anne-Marie M. van Roon, George E. Ghanim, Bilal Ahsan, Abraham O. Oluwole, Sew-Yeu Peak-Chew, Carol V. Robinson, Thi Hoang Duong Nguyen
Summary: Shelterin and nucleosomes interact at mammalian telomeres, but the mechanism is not yet understood. Cryo-electron microscopy was used to study the structure of a human telomeric nucleosome bound to the shelterin factor TRF1. The study revealed that TRF1 binds to unwrapped nucleosomal DNA ends by engaging both the DNA and the histone octamer, resulting in a shift in the nucleosomal DNA. Phosphorylation of TRF1 and a noncanonical DNA binding surface on TRF1 were found to be crucial for its association with telomeric nucleosomes. These findings provide important insights into shelterin-chromatin interactions and its roles at telomeres.
Article
Multidisciplinary Sciences
Luke Smithers, Oksana Degtjarik, Dietmar Weichert, Chia-Ying Huang, Coilin Boland, Katherine Bowen, Abraham Oluwole, Corinne Lutomski, Carol V. Robinson, Eoin M. Scanlan, Meitian Wang, Vincent Olieric, Moran Shalev-Benami, Martin Caffrey
Summary: This study investigates the structural changes of the enzyme apolipoprotein N-acyltransferase (Lnt) during its reaction. The study confirms the ping-pong mechanism of Lnt and explains the molecular basis for its ability to bind different substrates.