Article
Multidisciplinary Sciences
Radda Rusinova, Changhao He, Olaf S. Andersen
Summary: This study suggests that drugs can regulate membrane protein function by altering bilayer properties, involving both direct interactions with the protein and subtle mechanisms through changes in bilayer properties that impact protein conformation. Drug-induced regulation of membrane protein function involves a complex interplay of mechanisms, including both direct binding and bilayer-mediated effects.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Physiology
Rose E. Dixon
Summary: The organization and distribution of calcium channel clusters in cardiomyocytes are crucial for uniform contraction of myocardium. Signaling between these clusters generates Ca2+ sparks, which summate to produce global Ca2+ transients that activate the myofilaments for myocardial contraction. The heart responds to metabolic demands through altering calcium channel activity, and recent evidence suggests a role for dynamic reorganization of these channels in controlling myocardial function.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Dan Qiao, Himanshu Joshi, Huangtianzhi Zhu, Fushi Wang, Yang Xu, Jia Gao, Feihe Huang, Aleksei Aksimentiev, Jiandong Feng
Summary: Synthetic nanopores have been developed for applications in membrane filtration technologies and biomolecular sensing, but challenges remain in providing them with atomically defined shape and deliberate placement of chemical groups. A chemically defined transmembrane nanopore, EPM, demonstrates stable transmembrane transport functionality, particularly with up to 21-fold selectivity for potassium over sodium ions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Kirin D. Gada, Mengmeng Chang, Aishwarya Chandrashekar, Leigh D. Plant, Sami F. Noujaim, Diomedes E. Logothetis
Summary: G-protein-gated inwardly rectifying potassium (GIRK) channel activity is regulated by phosphatidylinositol-4,5-bisphosphate (PI 4,5P(2)), and PKC epsilon plays a role in the activation of GIRK channels in cardiac atrial cells and human stem cell-derived atrial cardiomyocytes. PKC epsilon enhances the interaction between GIRK4 and GIRK1/4 with PIP2, leading to increased channel activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Cell Biology
Andrea Jazmin Chiliquinga, Brenda Acosta, Ingrid Ogonaga-Borja, Fernanda Villarruel-Melquiades, Jaime de la Garza, Patricio Gariglio, Rodolfo Ocadiz-Delgado, Ana Ramirez, Yesennia Sanchez-Perez, Claudia M. Garcia-Cuellar, Cecilia Banuelos, Javier Camacho
Summary: The human papilloma virus (HPV) group consists of about 200 genetic types that show a particular affinity for epithelial tissues and can range from causing benign symptoms to developing into complex pathologies, such as cancer. Ion channels, responsible for ion flow across cell membranes, play important roles in human physiology but can also trigger channelopathies, including cancer, when their function or expression is altered. Dysregulation of ion channels has been observed in HPV-associated cancers, and understanding their dynamics may improve the diagnosis, prognosis, and treatment of these diseases.
Review
Pharmacology & Pharmacy
T. Crespo-Garcia, A. Camara-Checa, M. Dago, M. Rubio-Alarcon, J. Rapun, J. Tamargo, E. Delpon, R. Caballero
Summary: Cardiac electrical activity is regulated by ion channels, and transcription factors play a critical role in controlling this activity. They may serve as potential drug targets for treating cardiac arrhythmias.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Chemistry, Multidisciplinary
Chaoji Chen, Liangbing Hu
Summary: Ion transport and regulation in wood-based materials can be controlled through structural and compositional engineering from macroscale to nanoscale, enhancing their capability for multiple functions in emerging applications. Wood and its derivatives, with their unique ion regulation capability and renewable nature, are the natural choice of materials towards sustainability.
ADVANCED MATERIALS
(2021)
Review
Chemistry, Multidisciplinary
Eric C. R. McKenzie, Seyyedamirhossein Hosseini, Ana G. Couto Petro, Kelly K. Rudman, Benjamin H. R. Gerroll, Mohammad S. Mubarak, Lane A. Baker, R. Daniel Little
Summary: Electrosynthesis is a popular and green alternative to traditional methods, and understanding reaction mechanisms is crucial for process optimization. A variety of analytical tools are available to identify and quantify reaction products and intermediates. Technique selection depends on predicted reaction pathways and electrogenerated intermediates, often requiring a combination of methods for model accuracy.
Article
Biochemistry & Molecular Biology
Dominika Kozon, Piotr Bednarczyk, Adam Szewczyk, Dominik Janczewski
Summary: The study investigated the mechanisms of amphiphilic antimicrobial polymers on the bacterial cell membrane, revealing their ability to increase membrane permeability or rupture and promote ion transport through a unique mechanism. The activity was found to be strongly correlated with the polymer structure and Zeta potential.
Review
Biochemistry & Molecular Biology
Charlotte Van den Eynde, Joris Vriens, Katrien De Clercq
Summary: Calcium ions play a critical role in cell function, with transient receptor potential (TRP) channels serving as a type of ion channel that can convey various stimuli and potentially participate in cellular responses to changing environments.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Afeesh Rajan Unnithan, Arathyram Ramachandra Kurup Sasikala, Bishnu Kumar Shrestha, Alex Lincoln, Thomas Thomson, Alicia J. El Haj
Summary: Non-invasive approaches using remotely controllable nanomaterials, such as the developed GOMNP composite, have shown potential in enhancing treatment efficacy in regenerative medicine and tissue repair. Remote activation of mechanotransduction pathways through functionalized GOMNPs has led to enhanced bone formation.
ADVANCED FUNCTIONAL MATERIALS
(2022)
Article
Multidisciplinary Sciences
Leandro M. Alonso, Mara C. P. Rue, Eve Marder
Summary: Neurons use intracellular calcium concentrations to regulate their excitability, and models with multiple sensors can distinguish different activity patterns. However, previous models with multiple sensors displayed instabilities leading to unbounded growth of conductances. By introducing a nonlinear degradation term, we prevent conductances from growing beyond a certain bound. The modified model can recover from perturbations and shows that caution must be exercised in interpreting manipulations that mimic increased neuronal activity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Cell Biology
Afroditi Petsakou, Norbert Perrimon
Summary: Proper regulation of ion balance in the intestinal epithelium is crucial for physiological functions, while imbalance can lead to intestinal disorders with significant health consequences. Recent studies involving Drosophila gut have identified conserved molecular pathways linking regulators of Ca2+, Na+, and Cl- with intestinal stem cell proliferation, providing insights into bioelectrically induced proliferative responses. This review discusses the significance of these studies and emphasizes the advantages of using Drosophila to uncover conserved molecular pathways in the intestinal epithelium under different conditions.
TRENDS IN CELL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Hanggu Kim, Eunyoung Kim, Byoung-Cheol Lee
Summary: The N-terminus of TMEM16C determines its localization on the plasma membrane and affects its phospholipid scrambling activity. TMEM16C isoform 1 and isoform 3 transport phosphatidylserine to the cell surface, while isoform 2 does not possess this ability.
Article
Biochemistry & Molecular Biology
Zdena Palkova, Libuse Vachova
Summary: Single-celled yeasts form spatially structured populations in colonies and biofilms, either alone or in cooperation with other microorganisms. Understanding the complexities and diversity of these multicellular structures remains a challenge, with future emphasis on integrated multi-omics approaches and analysis of differentiated cell subpopulations.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
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
Chemistry, Multidisciplinary
Di Wu, Carol Robinson
Summary: Oligomerization and glycosylation play important roles in the stability and efficacy of therapeutic glycoproteins, but the interplay between these two attributes is often difficult to define. In this study, a native top-down mass spectrometry approach was used to assess the glycosylation status of therapeutic cytokine and hormone assemblies and to relate interfacial glycan occupancy to complex stability. The study found that interfacial O-glycan stabilizes tumor necrosis factor-alpha trimer, while interferon-beta 1a dimerization is independent of glycosylation. Furthermore, a unique distribution of N-glycans on the follicle-stimulating hormone alpha subunit was discovered, and the interfacial N-glycan was found to interact extensively with the beta subunit to regulate dimer assembly.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Medicinal
Lisbeth R. Kjolbye, Lars Sorensen, Jun Yan, Nils A. Berglund, Jesper Ferkinghoff-Borg, Carol V. Robinson, Birgit Schiott
Summary: This study used molecular dynamics simulations and native mass spectrometry to investigate the interaction between PI(4,5)P-2 lipids and GCGR, revealing differential affinities of the lipids to different conformations of GCGR. Furthermore, the study uncovered the role of a conserved binding site in stabilizing the inactive conformation of GCGR in class B GPCRs.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Multidisciplinary Sciences
Longfei Wang, Di Wu, Carol Robinson, Tian-Min Fu
Summary: This study identifies a new protein called mEAK-7 that interacts with V-ATPases and may regulate its function while also being involved in mTOR signaling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Hsin-Yung Yen, Idlir Liko, Wanling Song, Parth Kapoor, Fernando Almeida, Joanna Toporowska, Karolina Gherbi, Jonathan T. S. Hopper, Steven J. Charlton, Argyris Politis, Mark S. P. Sansom, Ali Jazayeri, Carol Robinson
Summary: This study presents a mass spectrometry-based approach to investigate the biased signaling and allosteric modulation of the beta(1)-adrenergic receptor in response to different ligands. The researchers discovered that isoprenaline can act as a biased agonist and that endogenous zinc ions enhance the binding between the receptor and G(s) proteins.
Article
Biochemistry & Molecular Biology
Philipp A. M. Schmidpeter, Di Wu, Jan Rheinberger, Paul M. Riegelhaupt, Haiping Tang, Carol Robinson, Crina M. Nimigean
Summary: Lipids play important roles in regulating membrane protein function. Anionic lipids were found to bind to bacterial pacemaker channel SthK and contribute to the activity of heart and brain pacemaker channel HCN2. Anionic lipids facilitate channel opening by destabilizing intracellular salt bridge interactions.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
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
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
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.
