Review
Biochemistry & Molecular Biology
Gregorio Fernandez-Ballester, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel
Summary: The thermoTRP family of ion channels, which includes multiple nonselective cation channels, are activated by physical and chemical stimuli, functioning as polymodal receptors. These channels undergo gating through changes in temperature, osmolarity, voltage, pH, pressure, and by chemical compounds that bind to the proteins. Recent advances in cryo-electron microscopy techniques have provided high-resolution structures of these channels in different states, shedding light on the underlying allosteric gating mechanisms. Understanding these mechanisms is important for the development of drug-based therapies for diseases involving dysfunctional thermoTRP channels, such as chronic pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Leo C. T. Ng, Brandon J. Harris, Megan Larmore, My C. Ta, Thuy N. Vien, Valerie L. Tokars, Vladimir Yarov-Yarovoy, Paul G. DeCaen
Summary: In this study, computational prediction tools were used to model missing PKD2L1 structural motifs and evaluate over 150 mutations in the entire pore module. Results revealed an energetic landscape of the polycystin pore and identified critical structural regulators controlling the conductive and nonconductive states of the polycystin ion channel.
Review
Biochemistry & Molecular Biology
Vanessa Judith Flegler, Tim Rasmussen, Bettina Boettcher
Summary: The ability to cope with and adapt to changes in the environment is essential for all organisms. This review discusses the current structural and functional models for the mechanically stimulated channel MscS, as well as the influence of certain membrane characteristics on gating.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Infectious Diseases
Evgeny G. Chulkov, Emery Smith, Claudia M. Rohr, Nawal A. Yahya, Sang-Kyu Park, Louis Scampavia, Timothy P. Spicer, Jonathan S. Marchant
Summary: This study optimized a high-throughput screening method for Schistosoma mansoni TRPMPZQ activity, leading to the discovery of a novel activator of Sm.TRPMPZQ and numerous potential blockers. The new activator, though distinct from PZQ, was similar to a known chemical entity identified through phenotypic screening.
PLOS NEGLECTED TROPICAL DISEASES
(2021)
Review
Biochemistry & Molecular Biology
Milena Duitama, Yurany Moreno, Sandra Paola Santander, Zulma Casas, Jhon Jairo Sutachan, Yolima P. Torres, Sonia L. Albarracin
Summary: Transient receptor potential (TRP) channels play a critical role in cancer-related pain. Substances released by the cancer microenvironment modulate the activity of TRP channels, affecting pain transmission. Secondary metabolites derived from plant extracts have the potential to serve as therapeutic agents for relieving cancer-induced pain.
Review
Neurosciences
Maria V. Yelshanskaya, Kirill D. Nadezhdin, Maria G. Kurnikova, Alexander I. Sobolevsky
Summary: This review discusses the molecular structure of the epithelial calcium channel TRPV6, highlighting its unique functional properties such as high Ca2+ selectivity and channel opening mechanism. The inhibitor 2-aminoethoxydiphenyl borate (2-APB) and calmodulin (CaM) play important roles in regulating TRPV6 activity.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
Zhengshan Hu, Xiangdong Zheng, Jian Yang
Summary: The study presents the structures of the cGMP-activated human cone photoreceptor CNGA3/CNGB3 channel in different states. The findings reveal the conformational trajectory of the channel and provide an expanded framework for studying CNG properties and channelopathy.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Rei Nishimoto, Sandra Derouiche, Kei Eto, Aykut Deveci, Makiko Kashio, Yoshitaka Kimori, Yoshikazu Matsuoka, Hiroshi Morimatsu, Junichi Nabekura, Makoto Tominaga
Summary: Microglia maintain central nervous system homeostasis by monitoring changes in their environment and taking protective actions, with their movement being modulated by temperature. This temperature-dependent movement may have potential clinical applications in preserving cell function.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Grigory Maksaev, Michael Bruendl-Jirout, Anna Stary-Weinzinger, Eva-Maria Zangerl-Plessl, Sun-Joo Lee, Colin G. Nichols
Summary: The authors introduced negative charges in Kir2.2 channels, resulting in pH-dependent sub-conductances. Molecular dynamics simulations show that protonation leads to step-wise alterations of ion pooling and conductance, appearing as gated substates. Single-channel recordings reveal pH-dependent subconductance behaviors.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Linus J. Conrad, Peter Proks, Stephen J. Tucker
Summary: This passage discusses a voltage-dependent gating process in the TREK-2 K+ channel, which can be modulated by small molecule agonists and high internal K+ concentrations. It is found that high ionic-strength can inhibit the channel conductance, while the activatory effect of BL1249 on channel open probability persists under these conditions. The influence of negatively charged activators like BL1249 on permeation is consistent with an electrostatic mechanism, suggesting complexity in their effect on channel gating.
Article
Multidisciplinary Sciences
Yuqi Qin, Daqi Yu, Dan Wu, Jiangqing Dong, William Thomas Li, Chang Ye, Kai Chit Cheung, Yingyi Zhang, Yun Xu, YongQiang Wang, Yun Stone Shi, Shangyu Dang
Summary: This study determines the cryo-EM structure of mouse TMEM63C and reveals its structural differences compared to other TMEM63 proteins. The coupling of TM0 and TM6 is shown to play important roles in channel activity. Additionally, it is discovered that TMEM63C exists primarily as a monomer, while TMEM63B can exist as a mixture of monomer and dimer, suggesting oligomerization as a regulatory mechanism.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Christophe Simard, Margaux Aize, Sebastien Chaigne, Harlyne Mpweme Bangando, Romain Guinamard
Summary: The role of ion channels in cardiac activity, morphological remodeling, and valve development and remodeling is discussed. Mutation in ion channel genes is observed in patients with malformation, such as bicuspid aortic valve. Ion channels are also involved in the morphological remodeling of valves, leading to aortic stenosis. Understanding the role of ion channels in the progression of aortic stenosis is crucial for developing new therapeutic approaches to avoid valve replacement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Philipp A. M. Schmidpeter, John T. Petroff, Leila Khajoueinejad, Aboubacar Wague, Cheryl Frankfater, Wayland W. L. Cheng, Crina M. Nimigean, Paul M. Riegelhaupt
Summary: Tandem pore (K2P) potassium channels are influenced by the composition of phospholipids in the bilayer, which can directly alter their gating. This study provides insight into the molecular details of lipid modulation in K2P channels, revealing two distinct pathways by which anionic lipids enhance channel activity. The findings contribute to a model that integrates lipid gating with the effects of other mechanosensitive K2P modulators.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Marcin Makowski, Victor G. Almendro-Vedia, Marco M. Domingues, Octavio L. Franco, Ivan Lopez-Montero, Manuel N. Melo, Nuno C. Santos
Summary: The designed AMP EcDBS1R4 kills Escherichia coli by membrane hyperpolarization and can interact with the phospholipid cardiolipin. It alters the membrane environment, impairing the interaction between cardiolipin and the peripheral stalk that binds the F-1 and F-O domains. This mechanism may inspire new research on the mode of action and design of other AMPs.
Review
Cell Biology
Goncalo Mesquita, Natalia Prevarskaya, Albrecht Schwab, V'yacheslav Lehen'kyi
Summary: TRP channels, a diverse superfamily of ion channels, have been implicated in various physiological processes and their potential role in cancer progression, particularly in pancreatic cancer, is being explored. This review analyzes existing knowledge on TRP channels in cancer, with a focus on potential therapeutic interventions for pancreatic ductal adenocarcinoma.