Article
Cell Biology
Xiaofei Wang, Yawen Li, Hong Wei, Zhisen Yang, Rui Luo, Yongxiang Gao, Wei Zhang, Xin Liu, Linfeng Sun
Summary: TRPA1 is an ion channel that responds to noxious temperature or chemical stimuli. The thermosensitivity of TRPA1 varies among different species or isoforms. This study determines the structures of a heat-sensitive isoform of TRPA1 in fruit flies and identifies conformational changes in the ankyrin repeat domain and coiled-coil domain. The findings provide insights into the gating mechanism of TRPA1.
Article
Biochemistry & Molecular Biology
Hao Chi, Xian Zhang, Xueqin Chen, Sui Fang, Qiang Ding, Zhaobing Gao
Summary: Sanguinarine, a benzyl isoquinoline alkaloid extracted from Papaveraceae plants, activates TRPA1 channel and increases excitability of mouse DRG neurons, resulting in nociceptive behaviors. Attenuation of excitability enhancement and nociceptive behaviors can be achieved by using TRPA1 channel antagonist or knockout of trpa1 gene.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Justyna B. Startek, Alina Milici, Robbe Naert, Andrei Segal, Yeranddy A. Alpizar, Thomas Voets, Karel Talavera
Summary: The study demonstrates that TRPA1 channel can sense non-electrophilic compounds by inducing mechanical perturbations in the cell membrane, leading to TRPA1 activation. Non-electrophilic alkylphenols enhance the activation potency of TRPA1 by increasing lipid order and membrane rigidity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Dinesh C. Indurthi, Anthony Auerbach
Summary: Receptors switch between resting and active shapes under the influence of agonists. The receptor's response depends on the difference in agonist binding energy. Efficiencies estimated from concentration-response curves show five discrete classes and linear correlation within each class. The conversion factor p links agonist binding with receptor gating and plays a role in the allosteric transition of the protein.
Article
Chemistry, Multidisciplinary
Wouter Engelen, Christian Sigl, Karoline Kadletz, Elena M. Willner, Hendrik Dietz
Summary: This study presents a strategy for controlling DNA nanodevices based on IgG antibodies sensing antigens, allowing for antigen-triggered disassembly and release of molecular payload. The method is applicable in various DNA nanostructures and IgG-antigen combinations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Jie Yu, Hongtao Zhu, Remigijus Lape, Timo Greiner, Juan Du, Wei Lu, Lucia Sivilotti, Eric Gouaux
Summary: Using electrophysiology and cryo-EM reconstructions, this study investigated the mechanism of partial agonist action on neurotransmitter receptors, revealing new conformational states along the receptor reaction pathway. The results demonstrated that partial agonists can occupy closed channel states bound by agonists, affecting the receptor channel's open probability.
Article
Biochemistry & Molecular Biology
David Manneck, Gisela Manz, Hannah-Sophie Braun, Julia Rosendahl, Friederike Stumpff
Summary: Research indicates the therapeutic potential of cinnamaldehyde in inflammatory bowel disease through activation of the TRPA1 channel and modulation of ion transport in the colon. Cinnamaldehyde may also influence cellular environments through different signaling pathways to prevent damage to colonic epithelium and microbiome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Karen V. Torres, Sebastian Pantke, Daniel Rudolf, Mirjam M. Eberhardt, Andreas Leffler
Summary: Naturally occurring coumarin osthole has anti-itch properties by inhibiting or desensitizing the TRPV1 and TRPV3 cation channels. Osthole is also found to activate TRPA1, but this effect is pruritic rather than anti-itch. Osthole is a potent non-electrophilic agonist of TRPA1, and the importance of this property for its anti-itch effects needs further exploration.
NEUROSCIENCE LETTERS
(2022)
Article
Chemistry, Medicinal
Balazs Zoltan Zsido, Rita Borzsei, Erika Pinter, Csaba Hetenyi
Summary: TRPA1 is a calcium ion channel protein that can be activated through various means, and recent experimental determinations of its apo and holo structures have provided insights into the binding dynamics with agonists. This has led to the development of a mechanism-based predictive model for identifying new binding sites.
Article
Biochemistry & Molecular Biology
Pragyanshu Khare, Neha Mahajan, Dhirendra Pratap Singh, Vibhu Kumar, Vijay Kumar, Priyanka Mangal, Ravneet K. Boparai, Adam Gesing, Sanjay K. Bhadada, Shyam S. Sharma, Kanthikiran Kondepudi, Kanwaljit Chopra, Mahendra Bishnoi
Summary: This study suggests that dietary TRPA1 agonist ARGJ can prevent metabolic complications induced by HFD. HFD leads to reduced gut TRPA1 expression and dysregulation of post-prandial gut hormone levels, resulting in hunger phenotype, altered glucose homeostasis, hepatic inflammation, and fat accumulation. TRPA1 agonism through ARGJ supplementation can prevent HFD-induced metabolic complications.
Article
Neurosciences
Chang Liu, Rebecca Reese, Simon Vu, Lionel Rouge, Shannon D. Shields, Satoko Kakiuchi-Kiyota, Huifen Chen, Kevin Johnson, Yu Patrick Shi, Tania Chernov-Rogan, Demi Maria Zabala Greiner, Pawan Bir Kohli, David Hackos, Bobby Brillantes, Christine Tam, Tianbo Li, Jianyong Wang, Brian Safina, Steve Magnuson, Matthew Volgraf, Jian Payandeh, Jie Zheng, Alexis Rohou, Jun Chen
Summary: A non-covalent agonist, GNE551, has been discovered to activate TRPA1 ion channel differently from covalent agonists, inducing persistent pain. The cryo-EM structure of the TRPA1-GNE551 complex reveals a distinct binding pocket and ligand-interaction mechanism. This biased agonism of TRPA1 has important implications for the development of effective drugs tailored to different disease etiologies.
Article
Chemistry, Multidisciplinary
Prashant Donthamsetti, David B. Konrad, Belinda Hetzler, Zhu Fu, Dirk Trauner, Ehud Y. Isacoff
Summary: G protein-coupled receptors (GPCRs) are common drug discovery targets, but the complexity of in vivo receptor activation has hindered drug development. Photopharmacology offers the potential to control drug action using light. Recent advances include a photoswitchable allosteric agonist that selectively activates receptors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Review
Chemistry, Multidisciplinary
Sebastian Acosta-Calle, Alexander J. M. Miller
Summary: The development of catalysts has had a significant impact on science and technology, allowing for optimized reaction conditions, improved catalytic activity, and selectivity. Controlled catalysis can be achieved by manipulating the dynamics of ligands and gating substrate access to the catalyst site. The design principles for cation-controlled catalysis have been explored and various catalysts have been developed for switchable and tunable catalysis.
ACCOUNTS OF CHEMICAL RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Andrea Saponaro, Daniel Bauer, M. Hunter Giese, Paolo Swuec, Alessandro Porro, Federica Gasparri, Atiyeh Sadat Sharifzadeh, Antonio Chaves-Sanjuan, Laura Alberio, Giacomo Parisi, Gabriele Cerutti, Oliver B. Clarke, Kay Hamacher, Henry M. Colecraft, Filippo Mancia, Wayne A. Hendrickson, Steven A. Siegelbaum, Dario DiFrancesco, Martino Bolognesi, Gerhard Thiel, Bina Santoro, Anna Moroni
Summary: The HCN1-4 channel family is crucial for controlling automaticity in cardiac and neuronal pacemaker cells by regulating the hyperpolarization-activated cation current I-f/I-h. Cryo-EM structures of HCN4 with or without bound cAMP show insights into ligand-induced transitions, while analysis of open/closed pore states reveals mechanisms of channel gating and ion permeation. These findings contribute to understanding HCN channel gating, cyclic nucleotide-dependent modulation, and ion permeation mechanisms.
Article
Multidisciplinary Sciences
Chen Liu, Lianping Shen, Yu Xiao, David Vyshedsky, Chao Peng, Xiang Sun, Zhiwen Liu, Lijun Cheng, Hua Zhang, Zhifu Han, Jijie Chai, Hen-Ming Wu, Alice Y. Cheung, Chao Li
Summary: This study elucidates the precise communication mechanism between pollen and pistil in angiosperms. Pollen competes with stigma peptides through binding, leading to a decrease in stigmatic ROS levels after pollination, facilitating pollen hydration and germination.
Article
Biochemistry & Molecular Biology
Aysenur Torun Yazici, Eleonora Gianti, Marina A. Kasimova, Bo-Hyun Lee, Vincenzo Carnevale, Tibor Rohacs
Summary: Regulation of the TRPV1 channel by phosphoinositides is complex, with PtdIns potentially acting as a competitive antagonist or activator depending on the presence of PtdIns(4,5)P-2. Different binding sites for phosphoinositides may explain the varied effects observed on TRPV1 activity.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Eleonora Gianti, Simona Percec
Summary: This Perspective outlines recent progress and future directions for using machine learning in the design, synthesis, processing, and characterization of biomacromolecules. It highlights the importance of using machine learning to extract relevant information from chemistry and biology fields to advance our understanding of chemical and biomolecular systems.
Article
Multidisciplinary Sciences
Willow Coyote-Maestas, David Nedrud, Antonio Suma, Yungui He, Kenneth A. Matreyek, Douglas M. Fowler, Vincenzo Carnevale, Chad L. Myers, Daniel Schmidt
Summary: The research conducted a large-scale, high-throughput biochemical assay to determine the compatibility of over 300,000 domain recombination variants of the inward rectifier K+ channel Kir2.1. They found that genomic and biophysical mechanisms acted together to favor gain of large, structured domains at protein termini during ion channel evolution.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Francisco McGee, Sandro Hauri, Quentin Novinger, Slobodan Vucetic, Ronald M. Levy, Vincenzo Carnevale, Allan Haldane
Summary: Generative models, such as Potts models and VAEs, are increasingly popular in protein design, but lack rigorous metrics for comparison. Current evaluation metrics do not clearly assess whether generative protein sequence models faithfully reproduce the complex multi-residue mutational patterns observed in natural sequences due to epistasis. New sequence statistics were developed to assess the generative capacity of existing GPSMs, with the Potts model showing the largest capacity to replicate natural sequences.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Ravi Patel, Vincenzo Carnevale, Sudhir Kumar
Summary: Research has shown that negative selection between sites creates more invariant sites compared to site-specific preferences alone, with an increasing role over longer evolutionary periods. These findings highlight the mechanistic role of epistasis in site invariance and evolutionary rates.
MOLECULAR BIOLOGY AND EVOLUTION
(2022)
Article
Biology
Deny Cabezas-Bratesco, Francisco A. Mcgee, Charlotte K. Colenso, Kattina Zavala, Daniele Granata, Vincenzo Carnevale, Juan C. Opazo, Sebastian E. Brauchi
Summary: Transient receptor potential (TRP) proteins are a diverse family of cation-selective channels, with detailed mechanisms of regulation still under debate. Through analysis, a highly conserved set of residues was discovered in TRP channels, positioned at equivalent locations in different subtypes, potentially influencing coupling strategies of various subgroups.
Article
Biochemistry & Molecular Biology
Siyuan Zhao, Vincenzo Carnevale, Matthew Gabrielle, Eleonora Gianti, Tibor Rohacs
Summary: TRPM3 is a heat-activated ion channel that depends on PI(4,5)P-2 for its activity. Mutating residues involved in PI(4,5)P-2 binding increases sensitivity to TRPM3 inhibition. Additionally, PI(4,5)P-2 is involved in the regulation of TRPM8 and the inhibition by G beta gamma. Disease-associated gain-of-function TRPM3 mutations do not increase sensitivity to PI(4,5)P-2.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Chemistry, Physical
Ruiyu Wang, Yunqian Zou, Richard C. Remsing, Naomi O. Ross, Michael L. Klein, Vincenzo Carnevale, Eric Borguet
Summary: Understanding the microscopic driving force of water wetting is challenging and important for material design. This study investigates the relations between structure, dynamics and hydrogen bonds of interfacial water on alumina surfaces using molecular dynamics simulations and experiments. The findings reveal superhydrophilicity of both surfaces, with the (0001) surface being more hydrophilic. The molecular dynamics simulations eliminate surface contamination and provide insights into the microscopic origin of the macroscopic superhydrophilicity: strong water-to-aluminol hydrogen bonds.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Chemistry, Multidisciplinary
Shaohua Zhang, Wei Li, Jiabin Luan, Abhinav Srivastava, Vincenzo Carnevale, Michael L. Klein, Jiawei Sun, Danni Wang, Serena P. Teora, Sjoerd J. Rijpkema, Johannes D. Meeldijk, Daniela A. Wilson
Summary: Researchers report an adaptive non-covalent binding strategy for surface functionalization using a hydrophobic anchor to insert into a poly(ethylene glycol) (PEG) host. This strategy allows for spontaneous loading of hydrophilic charged and non-charged functional modules onto the PEG surface without the need for catalysts or binding groups. The reversible insertion of the hydrophobic anchor enables programmable surface functionalization, challenging the current understanding of PEG in hydrophilicity and potentially advancing nanomedicine, advanced materials, and nanotechnology.
Article
Physics, Multidisciplinary
Antonio Suma, Vincenzo Carnevale, Cristian Micheletti
Summary: Using theory and simulations, the authors studied DNA unzipping via nanopore translocation and found three dynamical regimes depending on the applied force. They showed that the normal regime can be modeled as a one-dimensional stochastic process and used the theory of stochastic processes to recover the free-energy landscape. This approach can be applied to other single-molecule systems with periodic potentials to obtain detailed free-energy landscapes from out-of-equilibrium trajectories.
PHYSICAL REVIEW LETTERS
(2023)
Article
Chemistry, Medicinal
Phu K. Tang, Prabir Khatua, Vincenzo Carnevale, Sharon M. Loverde
Summary: In this study, the initial stages of self-assembly of a model drug amphiphile in an aqueous solution were characterized through atomistic molecular dynamics simulations. It was found that aromatic stacking of the drug molecules drove the formation of a higher-density liquid droplet, which elongated and formed a higher-ordered supramolecular assembly through reorganization and additional aromatic stacking. The development of novel reaction coordinates tailored to this class of molecules was shown to be essential in capturing the degree of molecular order during assembly. This approach can be extended to study the supramolecular assembly pathway of other molecules containing aromatic compounds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Physical
Mohsen Farshad, Mark J. DelloStritto, Antonio Sum, Vincenzo Carneval
Summary: In this study, we analyzed a methanol/hexane mixture to investigate the phase diagram and structural changes associated with demixing. We found that the topological properties of the H-bond network abruptly change as the system crosses the demixing line, which can be detected using spectral clustering. We further validated the effectiveness of spectral clustering analysis in detecting demixing transitions in a Lennard-Jones system without H-bonds.
JOURNAL OF PHYSICAL CHEMISTRY B
(2023)
Article
Chemistry, Medicinal
Phu K. Tang, Prabir Khatua, Vincenzo Carnevale, Sharon M. Loverde
Summary: The initial stages of self-assembly of a model drug amphiphile in an aqueous solution were characterized using atomistic molecular dynamics simulations. Two-dimensional metadynamics calculations were performed to understand the assembly space of the model drug amphiphile Tubustecan, TT1. Aromatic stacking of the hydrophobic anticancer drug, Camptothecin (CPT), was found to drive the formation of a higher-density liquid droplet, which elongates and forms a higher-ordered supramolecular assembly through reorganization and additional aromatic stacking of the drugs. Novel reaction coordinates tailored to this class of molecules were shown to be essential in capturing the underlying degree of molecular order during assembly. This approach can be further refined and extended to study the supramolecular assembly pathway of other molecules containing aromatic compounds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Multidisciplinary
Shaohua Zhang, Abhinav Srivastava, Wei Li, Sjoerd J. Rijpkema, Vincenzo Carnevale, Michael L. Klein, Daniela A. Wilson
Summary: An adaptive surface that can detect and respond to environmental changes is crucial for smart functional materials. This study presents a pH-responsive anchoring system on the poly(ethylene glycol) (PEG) corona of polymer vesicles. By reversibly protonating the covalently linked pH-sensing group, the hydrophobic anchor pyrene can be inserted into the PEG corona. The pH-responsive region can be engineered from acidic to neutral and basic conditions depending on the sensor's pKa. The switchable electrostatic repulsion between the sensors contributes to the responsive anchoring behavior. These findings offer a new responsive binding chemistry for the development of smart nanomedicine and nanoreactors.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)