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
Biochemistry & Molecular Biology
Marco Colombini, Kevin Barnes, Kai-Ti Chang, Muhsin H. Younis, Vicente M. Aguilella
Summary: Gram-negative bacteria have a variety of channel-forming proteins in their outer membrane, some of which show voltage dependence. Triplin, a trimeric channel former, has steep voltage dependence and high inter-subunit cooperativity. Detailed molecular insights into these unusual properties have been obtained at the single-molecule level.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
Biochemistry & Molecular Biology
Marco Colombini, Patrick Liu, Chase Dee
Summary: The outer membrane of Gram-negative bacteria contains voltage-dependent pore-forming structures called porins. Triplin, a novel bacterial pore-former, is a three-pore structure with a highly voltage-dependent and complex gating process. The closure of the three pores occurs sequentially, with each pore closing at different electric potentials. The closure mechanism involves the translocation of a positive domain through the membrane, blocking the pore and resulting in its closed conformation. Kinetic measurements support this mechanism by showing that the translocation occurs while the voltage sensor travels through most of the transmembrane voltage.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Multidisciplinary Sciences
Takushi Shimomura, Kiichi Hirazawa, Yoshihiro Kubo
Summary: This study reveals that different conformations of DII-S4 determine the gating modes in Two-pore channels (TPCs), with the intermediate state representing the PIP2-gating mode. TPC3 is primarily voltage-dependent, while TPC2 is PIP2-gated and nonvoltage-dependent. Furthermore, the antidepressant desipramine induces voltage dependence in TPC2, and the flavonoid naringenin biases the mode preference from PIP2-gating to desipramine-induced voltage gating.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Simon Scheuring
Summary: This study derives the forces and energies involved in the gating process of tetrameric cation channels using a physical model and MthK structures. It is found that the conformational change in the RCK domain of MthK opens the bundle-crossing gate through pulling via unfolded linkers. The linkers serve as entropic springs between the RCK domain and gate, storing potential energy and exerting pulling force to keep the gate open.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Rong Shen, Yilin Meng, Benoit Roux, Eduardo Perozo
Summary: This study investigates the conformational changes in voltage-sensing domains (VSDs) during the voltage activation process. Through molecular dynamics simulations and experimental validations, the researchers identified four different conformations visited in the VSD of the phosphatase Ci-VSP. The results provide insights into the energetics and mechanism of voltage activation in VSDs.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Claire C. Munier, Christian Ottmann, Matthew W. D. Perry
Summary: The 14-3-3 proteins play crucial roles in regulating the inflammatory response at genetic, molecular, and cellular levels. They affect key components of the immune response and can lead to clinical syndromes when their recognition processes are disrupted. Abnormal levels of 14-3-3 contribute to undesirable immune responses and chronic inflammatory conditions.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Loes M. Stevers, Madita Wolter, Graeme W. Carlile, Dwight Macdonald, Luc Richard, Frank Gielkens, John W. Hanrahan, David Y. Thomas, Sai Kumar Chakka, Mark L. Peterson, Helmut Thomas, Luc Brunsveld, Christian Ottmann
Summary: This study identified a macrocycle compound that stabilizes the interaction between mutant CFTR and the chaperone-like protein 14-3-3, rescuing its biological function.
NATURE COMMUNICATIONS
(2022)
Review
Cell Biology
Hua-Qian Yang, Fabio A. Echeverry, Assmaa ElSheikh, Ivan Gando, Sophia Anez Arredondo, Natalie Samper, Timothy Cardozo, Mario Delmar, Show-Ling Shyng, William A. Coetzee
Summary: Sarcolemmal/plasmalemmal ATP-sensitive K+ (K-ATP) channels play crucial roles in various cell types and tissues. Recent studies have highlighted that the surface expression of K-ATP channels is tightly regulated and has significant implications in both health and disease.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Review
Physics, Multidisciplinary
Joao Luis Carvalho-de-Souza, Andrea Saponaro, C. A. Z. Bassetto, Oliver Rauh, Indra Schroeder, Fabio Franciolini, Luigi Catacuzzeno, Francisco Bezanilla, Gerhard Thiel, Anna Moroni
Summary: This article summarizes recent advancements in understanding the mechanisms of ion permeation and gating in channel proteins, focusing on the elementary steps of ion transport through the pore and non-canonical modes of intramolecular communication between peripheral sensory domains and the central channel pore.
ADVANCES IN PHYSICS-X
(2022)
Article
Biology
Shuo Han, Sophia Peng, Joshua Vance, Kimberly Tran, Nhu Do, Nauy Bui, Zhenhua Gui, Shizhen Wang
Summary: This article investigates the conformational dynamics and gating mechanisms of voltage-gated proton (Hv) channels. By using single-molecule fluorescence resonance energy transfer (smFRET) with purified human voltage-gated proton (hHv1) channels reconstituted in liposomes, the real-time conformational trajectories of the S4 segment were observed. The results demonstrate that voltage and pH gradient can shift the conformational dynamics of the S4 segment, controlling the gating of the channel. The authors propose a kinetic model to explain the voltage and pH gating mechanisms in Hv channels, which may have implications for understanding the voltage sensing and gating in other voltage-gated ion channels.
Article
Biology
Xiaoan Wu, Marta E. Perez, Sergei Yu Noskov, H. Peter Larsson
Summary: Research demonstrates that KCNE1 regulates the function of potassium channel KCNQ1 by modulating the coupling between the voltage-sensing domain and pore domain through induced rotation. This rotation leads to residue clashes that prevent the formation of a conductive intermediate state conformation of the voltage sensor.
COMMUNICATIONS BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Andrew Bogard, Pangaea W. Finn, Aviana R. Smith, Ilinca M. Flacau, Rose Whiting, Daniel Fologea
Summary: The voltage regulation of lysenin channels in artificial lipid membranes leads to hysteresis, bistability, and memory. The presence of Cu2+ ions strengthens the hysteresis behavior and prevents the reopening of closed channels, reinstating the voltage gating and memory of lysenin channels.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Julian Alexander Schreiber, Anastasia Derksen, Gunnar Goerges, Sven Schuette, Jasmin Soergel, Aytug K. Kiper, Nathalie Strutz-Seebohm, Tobias Ruck, Sven G. Meuth, Niels Decher, Guiscard Seebohm
Summary: It is reported that the drug cloxyquin activates the TWIK-related spinal cord K+ channel (TRESK) by stabilizing the inner selectivity filter. This finding has significant implications for future drug development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Cell Biology
Anja J. Engel, Marina Kithil, Markus Langhans, Oliver Rauh, Matea Cartolano, James L. Van Etten, Anna Moroni, Gerhard Thiel
Summary: The study found that biased frequency of synonymous codons can affect protein localization within cells, thus modulating protein function through different steps such as transcription, translation, and folding.
Review
Physics, Multidisciplinary
Joao Luis Carvalho-de-Souza, Andrea Saponaro, C. A. Z. Bassetto, Oliver Rauh, Indra Schroeder, Fabio Franciolini, Luigi Catacuzzeno, Francisco Bezanilla, Gerhard Thiel, Anna Moroni
Summary: This article summarizes recent advancements in understanding the mechanisms of ion permeation and gating in channel proteins, focusing on the elementary steps of ion transport through the pore and non-canonical modes of intramolecular communication between peripheral sensory domains and the central channel pore.
ADVANCES IN PHYSICS-X
(2022)
Article
Physiology
Dominique Tandl, Tim Sponagel, Dalia Alansary, Sebastian Fuck, Timo Smit, Stephanie Hehlgans, Burkhard Jakob, Claudia Fournier, Barbara A. Niemeyer, Franz Roedel, Bastian Roth, Anna Moroni, Gerhard Thiel
Summary: This study reveals that X-ray irradiation can activate blood immune cells through inducing oscillations of cytosolic Ca2+ concentration and promoting the expression of transcription factor NFAT, which has implications for the toxicity and therapeutic effects of radiation therapy.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Oliver Rauh, Jennifer Opper, Maximilian Sturm, Nils Drexler, Deborah D. D. Scheub, Ulf-P. Hansen, Gerhard Thiel, Indra Schroeder
Summary: Most potassium channels have two gate locations, an inner gate and a filter gate, and the function of these gates is coupled in many channels. This study focuses on the filter gate of the viral channel KcvNTS and investigates its opening and closing mechanisms through single-channel recordings and gating analysis. The results show that mutations can affect the closing speed of the filter gate, and the coupling between the filter gate and surrounding structures may rely on different modes of interaction. Quantitative analysis suggests a concerted action of subunits in the energy barrier for filter closure.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Editorial Material
Biology
Neil L. Harrison, Geoffrey W. Abbott, Martina Gentzsch, Andrei Aleksandrov, Anna Moroni, Gerhard Thiel, Stephen Grant, Colin G. Nichols, Henry A. Lester, Andreas Hartel, Kenneth Shepard, David Cabrera Garcia, Masayuki Yazawa
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Sebastian Hoeler, Daniel Degreif, Florentine Stix, Shang Yang, Shiqiang Gao, Georg Nagel, Anna Moroni, Gerhard Thiel, Adam Bertl, Oliver Rauh
Summary: Researchers engineered baker's yeast to produce retinal and used it for screening of ChR2 protein function. They found that light activation of ChR2 increased sodium influx and inhibited cell growth, and in a potassium uptake-deficient yeast strain, growth could be rescued by the blue light-induced K+ conductance of ChR2. This study provides a simple and convenient method for screening new functional ChR2 variants.
Article
Physiology
Jan H. Krumbach, Daniel Bauer, Atiyeh Sadat Sharifzadeh, Andrea Saponaro, Rene Lautenschlaeger, Kristina Lange, Oliver Rauh, Dario DiFrancesco, Anna Moroni, Gerhard Thiel, Kay Hamacher
Summary: The authors used molecular dynamics simulations to study the interactions between monovalent cations and the HCN4 channel, and found that cation selectivity is determined by an adaptation of the cations to the filter structure. This study is important for understanding biological processes such as heartbeat and neuronal firing.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Cell Biology
Anja J. Engel, Steffen Paech, Markus Langhans, James L. van Etten, Anna Moroni, Gerhard Thiel, Oliver Rauh
Summary: When the K+ channel-like protein Kesv from Ectocarpus siliculosus virus 1 is expressed in mammalian cells, it is targeted to the mitochondria. By altering codon usage or inserting hydrophobic amino acids into the protein's C-terminal transmembrane domain, the targeting can be redirected to the endoplasmic reticulum (ER). Positive charge in the inserted amino acid triplet serves as a strong signal for mitochondria sorting, while a combination of hydrophilic amino acids and rarely used codons favors mitochondria sorting in cases of neutral amino acid triplets. Sorting to the ER is influenced by the inverse dependency. The data suggest that local changes in elongation velocity and co-translational folding in the C-terminal transmembrane domain can influence intracellular protein sorting.
Article
Cell Biology
Daniel Bauer, Jan Wissmann, Anna Moroni, Gerhard Thiel, Kay Hamacher
Summary: In this study, we used umbrella sampling to investigate the conduction of potassium and sodium in the HCN4 channel. Our findings suggest that the high energetic barriers inside the selectivity filter of this channel contribute to its low unitary conductance and weak selectivity. Additionally, we provide a thermodynamic explanation for the weak cation selectivity of HCN channels, which relies on sodium as a weak blocker that can only be released by potassium.
Meeting Abstract
Biophysics
Laura Cantu, Elena Del Favero, Anna Moroni, Ulrich Schubert, Caterina Ricci
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Meeting Abstract
Biophysics
Andrea Saponaro, Daniel Bauer, Hunter M. Giese, Antonio Chavez-Sanjuan, Ermanno Uboldi, Martino Bolognesi, Bina Santoro, Anna Moroni
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
Meeting Abstract
Biophysics
Andrea Saponaro, Daniel Bauer, Hunter Giese, Paolo Swuec, Alessandro Porro, Federica Gasparri, Atiyeh Sadat Sharifzadeh, Antonio Chaves-Sanjuan, Ermanno Uboldi, Anastasia Polyakova, Martino Bolognesi, Gerhard Thiel, Bina Santoro, Anna Moroni
EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS
(2021)
