Article
Cell Biology
Jiangtao Zhang, Shiqi Liu, Junping Fan, Rui Yan, Bo Huang, Feng Zhou, Tian Yuan, Jianke Gong, Zhu Huang, Daohua Jiang
Summary: In this study, cryoelectron microscopy was used to obtain structures of the Slo2.2 channel in closed, open, and inhibitor-bound form, providing insights into its cation regulation and inhibition. The closed state of Slo2.2 contains multiple K+ and Zn2+ binding sites in the cytoplasmic gating ring domain, which stabilize the closed conformation. The open state reveals Na+-sensitive sites that induce gating ring expansion and rotation upon Na+ binding, leading to inner gate opening. Additionally, a potent inhibitor blocks the pore by binding to a pocket formed by the pore helix and S6 helix. These findings establish a structural framework for studying Slo2.2 channel gating, Na+ sensation, and inhibition.
Article
Chemistry, Multidisciplinary
Ping Duan, Yaping Wang, Lichuan Chen, Kai Qu, Junyang Liu, Qian-Chong Zhang, Zhong-Ning Chen, Wenjing Hong
Summary: Investigating the correlations of electron transport between multiple channels shows promise for the design of molecule-scale circuits with logic operations. The modulation of electronegativity provides an effective method for controlling electron transport through multiple channels and exploring their interactions. Experimental and theoretical studies suggest that electronegativity has a more significant effect on electron transport in dual-channel structures.
Article
Biophysics
Mindaugas Snipas, Lukas Gudaitis, Lina Kraujaliene, Tadas Kraujalis, Vytas K. Verselis
Summary: The advancement of patch-clamp technique provides a powerful means to study the behaviors of ion channels. However, the recordings of gap junction (GJ) channels face unique challenges due to their intercellular configuration and natural clustering. This study proposes a methodology combining a four-state model (4SM) and maximum likelihood estimation (MLE) for reliable analysis of GJ channel currents.
BIOPHYSICAL JOURNAL
(2023)
Article
Multidisciplinary Sciences
Yoshiaki Kise, Go Kasuya, Hiroyuki H. Okamoto, Daichi Yamanouchi, Kan Kobayashi, Tsukasa Kusakizako, Tomohiro Nishizawa, Koichi Nakajo, Osamu Nureki
Summary: Mechanisms of modulation of Kv4 channel complexes by auxiliary subunits are central to the physiological function of channels in the brain and heart. The structures of Kv4.2-KChIP1 and Kv4.2-DPP6S complexes reveal that KChIP1 prevents N-type inactivation and stabilizes the S6 conformation, while DPP6S interacts with the S1 and S2 helices to accelerate voltage-dependent movement. KChIP1 and DPP6S do not directly interact with each other in the ternary complex, suggesting two distinct modes of modulation contribute to evoke A-type currents.
Article
Chemistry, Multidisciplinary
Mengchen Zhang, Chao Xing, Jianan Huang, Peishan Li, Long Jiang, Lingfeng Liu, Jianbo Jia, Xiwang Zhang, Shanqing Zhang, Changyu Liu
Summary: This study introduces a novel approach to controlling channel expansion using biomimetic adaptive aggregates, allowing for reversible regulation of channel size and charge and achieving programmable separation performance. This work is of great importance for the engineering of intelligent stimuli-responsive 2D nanofluidic channels.
ADVANCED FUNCTIONAL MATERIALS
(2023)
Article
Cell Biology
Gaoxingyu Huang, Dongliang Liu, Weipeng Wang, Qiurong Wu, Jiaofeng Chen, Xiaojing Pan, Huaizong Shen, Nieng Yan
Summary: This study reports the cryo-EM structure of Na(v)1.7 channel complexed with different subunits, revealing conformational differences and ligand-induced structural changes.
Article
Biochemistry & Molecular Biology
Diego J. B. Orts, Manoel Arcisio-Miranda
Summary: Voltage-gated proton channels (H(V)1) play crucial roles in various physiological processes, while glycosaminoglycans can modulate membrane receptors and ion channels. Defective biosynthesis of chondroitin sulfate and heparan sulfate in CHO-745 cells leads to gating alterations in the H(V)1 channel, affecting the coupling between voltage- and Delta pH-sensing.
Article
Biochemistry & Molecular Biology
Kathleen Elverson, Sally Freeman, Forbes Manson, Jim Warwicker
Summary: Many transmembrane proteins are modulated by intracellular or extracellular pH. Mutagenesis guided by amino-acid conservation and structure can be used to investigate pH dependence, but prediction of pKas can streamline this process. The hypothesis of modulation of calcium/proton coupling and pH-dependent activity through the extent of structural relaxation applies to various proteins, including bestrophin 1, TMEM16A, calmodulin, and calbindin D9k. Predicting altered pH dependence for mutations in ion channel disorders can support experimental studies and clinical intervention.
Article
Pharmacology & Pharmacy
Md Zubayer Hossain Saad, Liuruimin Xiang, Yan-Shin Liao, Leah R. Reznikov, Jianyang Du
Summary: The study identified molecular determinants responsible for the pH regulation of TRPM3, showing that both intracellular and extracellular protons block TRPM3 through binding sites in the pore region. Specific residue D1073 was found to be essential for pH sensitivity in TRPM3 channel.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Physiology
Vishwanath Jogini, Morten O. Jensen, David E. E. Shaw
Summary: This article presents the results of long-timescale molecular dynamics simulations to describe the lipid-dependent gating and spermine-induced inward rectification of the inward-rectifier potassium channel Kir2.2. PIP2 binding increases the stability of the channel in its open and conducting state, while spermine binds to a site located between the pore cavity and the selectivity filter. Additionally, charged residues in the cytoplasmic domain modulate conduction and rectification through finely tuned charge density.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Developmental Biology
Benjamin J. Smith, Patrice D. Cote, Francois Tremblay
Summary: The study demonstrates that Na(v)1.6 channels play a significant role in photoreceptor function during mouse eye development, with modulation through activity-dependent retinal ganglion cell axonal signaling targeting TrkB receptors. Blocking Na(v) channels or prolonged dark adaptation can reduce photoreceptor function, but restoration is possible with a TrkB receptor agonist, highlighting the transient nature of Na(v)-dependent modulation on photoreceptor function postnatal day 16.
DEVELOPMENTAL NEUROBIOLOGY
(2021)
Article
Cell & Tissue Engineering
Ieva Antanaviciute, Linas Simatonis, Orestas Ulcinas, Ausra Gadeikyte, Brigita Abakeviciene, Sigitas Tamulevicius, Valeryia Mikalayeva, Vytenis Arvydas Skeberdis, Edgaras Stankevicius, Tomas Tamulevicius
JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE
(2018)
Article
Biochemistry & Molecular Biology
Vytautas Raskevicius, Vaidas Jotautis, Lina Rimkute, Alina Marandykina, Mintaute Kazokaite, Visvaldas Kairys, Vytenis Arvydas Skeberdis
BIOSCIENCE REPORTS
(2018)
Review
Medicine, General & Internal
Ieva Antanaviciute, Paulius Gibieza, Rytis Prekeris, Vytenis Arvydas Skeberdis
MEDICINA-LITHUANIA
(2018)
Article
Biochemistry & Molecular Biology
Valeryia Mikalayeva, Ieva Cesleviciene, Ieva Sarapiniene, Vaidotas Zvikas, Vytenis Arvydas Skeberdis, Valdas Jakstas, Sergio Bordel
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Multidisciplinary Sciences
Eric Peterman, Paulius Gibieza, Johnathon Schafer, Vytenis Arvydas Skeberdis, Algirdas Kaupinis, Mindaugas Valius, Xavier Heiligenstein, Ilse Hurbain, Graca Raposo, Rytis Prekeris
NATURE COMMUNICATIONS
(2019)
Article
Biochemistry & Molecular Biology
Eun Ju Choi, Nicolas Palacios-Prado, Juan C. Saez, Jinu Lee
Article
Biochemistry & Molecular Biology
Ximena Lopez, Rosalba Escamilla, Paola Fernandez, Yorley Duarte, Fernando Gonzalez-Nilo, Nicolas Palacios-Prado, Agustin D. Martinez, Juan C. Saez
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Article
Medicine, Research & Experimental
Rokas Mickus, Gintare Janciuke, Vytautas Raskevicius, Valeryia Mikalayeva, Inga Matulyte, Mindaugas Marksa, Kestutis Maciunas, Jurga Bernatoniene, Vytenis Arvydas Skeberdis
Summary: This study identified nutmeg essential oil (NEO) and its constituents as potent inhibitors of Cx43 gap junctions by a slow gating mechanism. Additionally, NEO was found to reduce Novikoff hepatoma cell viability, proliferation, and colony formation capability at higher doses, but this effect was unrelated to its impact on gap junction dependent intercellular communication.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cell Biology
Paulius Gibieza, Eric Peterman, Huxley K. Hoffman, Schuyler Van Engeleburg, Vytenis Arvydas Skeberdis, Rytis Prekeris
Summary: The study identified Rab14 as a novel regulator of cytokinesis that contributes to the efficiency of recruiting Rab11-endosomes to the thin intracellular bridge (ICB) microtubules and affects actin clearance at the abscission site. Furthermore, Rab14 was found to bind to microtubule minus-end interacting MACF2/CAMSAP3 complex, influencing the targeting of endosomes to the ICB microtubules during cytokinesis.
MOLECULAR BIOLOGY OF THE CELL
(2021)
Article
Multidisciplinary Sciences
Ximena Lopez, Nicolas Palacios-Prado, Juan Guiza, Rosalba Escamilla, Paola Fernandez, Jose L. Vega, Maximiliano Rojas, Valeria Marquez-Miranda, Eduardo Chamorro, Ana M. Cardenas, Maria Constanza Maldifassi, Agustin D. Martinez, Yorley Duarte, Fernando D. Gonzalez-Nilo, Juan C. Saez
Summary: This study identified S394 as a potential phosphorylation site for CaMKII in Panx1 channels, showing that phosphorylation at this site may activate Panx1 channels, allowing for ATP release and DAPI uptake. The results suggest a mechanism for Panx1 activation in response to increased cytoplasmic calcium signals without cleavage of the C-terminal domain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Fernando Santos-Beneit, Vytautas Raskevicius, Vytenis A. Skeberdis, Sergio Bordel
Summary: Using Flux Balance Analysis, key human metabolic enzymes for therapeutic intervention against COVID-19 were identified, with potential inhibitors predicted. Promising molecules such as Triacsin C and Celgosivir showed effectiveness against various viruses. Other drugs targeting lipid metabolism, carbohydrate metabolism, or protein palmitoylation were also proposed.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Valeryia Mikalayeva, Monika Pankeviciute, Vaidotas Zvikas, V. Arvydas Skeberdis, Sergio Bordel
Summary: The degradation of branched chain amino acids serves as an important energy and carbon source for the proliferation of some cancer cells, providing a potential therapeutic target.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Physiology
Tadas Kraujalis, Lukas Gudaitis, Lina Kraujaliene, Mindaugas Snipas, Nicolas Palacios-Prado, Vytas K. Verselis
Summary: Electrical synapses formed by the connexin36 (Cx36) gap junction (GJ) channel protein play a significant role in the mammalian central nervous system. This study investigates the impact of amino acid substitutions in the N-terminal (NT) domain of Cx36 GJs on their modulation by intracellular Mg2+. The results suggest that Mg2+ binding to and stabilization of the closed state in each hemichannel is the most likely mechanism for Mg2+ modulation of Cx36 GJ, and the NT domain may be involved in the coupling of conformational changes between the NT and extracellular E1 domains.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Nicolas Palacios-Prado, Paola A. Soto, Ximena Lopez, Eun Ju Choi, Valeria Marquez-Miranda, Maximiliano Rojas, Yorley Duarte, Jinu Lee, Fernando D. Gonzalez-Nilo, Juan C. Saez
Summary: The study revealed that Pannexin1 forms cell-cell channels with distinct phenotypes and properties, exhibiting high conductivity and sensitivity to voltage and temperature; bioinformatics studies suggested that arginine residues inside the channel pore may be neutralized by hydrophobic interactions, allowing the passage of certain substances.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Ke-Jun Han, Valeryia Mikalayeva, Scott A. Gerber, Arminja N. Kettenbach, Vytenis A. Skeberdis, Rytis Prekeris
Summary: Rab40c protein was found to regulate the number, size, and distribution of focal adhesions in mammalian cells through ubiquitination. Rab40c interacts with protein phosphatase 6 (PP6) complex and ubiquitinates one of its subunits, ANKRD28, leading to lysosomal degradation. Knock-out cells show decreased phosphorylation of FAK and MOB1, which may contribute to the regulation of focal adhesions by Rab40c.
LIFE SCIENCE ALLIANCE
(2022)