Article
Multidisciplinary Sciences
Hanbin Jeong, Sarah Clark, April Goehring, Sepehr Dehghani-Ghahnaviyeh, Ali Rasouli, Emad Tajkhorshid, Eric Gouaux
Summary: This study reports the structure of the native TMC-1 mechanosensory transduction complex isolated from Caenorhabditis elegans. The complex is composed of TMC-1 subunits, CALM-1 calcium-binding protein, and TMIE transmembrane inner ear protein. CALM-1 makes extensive contacts with the TMC-1 subunits, while TMIE resides on the periphery of the complex.
Article
Pharmacology & Pharmacy
Kelsey C. North, Man Zhang, Aditya K. Singh, Dasha Zaytseva, Alexandria Slayden, Anna N. Bukiya, Alex M. Dopico
Summary: This study reveals that inhibition of calcium/voltage-gated BK channels by membrane cholesterol requires physiological levels of internal calcium (Ca2+) and is selectively linked to high-affinity Ca2+-sensing sites located in the cytosolic tail domain.
MOLECULAR PHARMACOLOGY
(2022)
Article
Biology
Janice M. Reimer, Morgan E. DeSantis, Andres E. Leschziner, Samara L. Reck-Peterson
Summary: This study reports the cryo-EM structures of human dynein-LIS1 complexes, revealing the differences between yeast and human systems. It provides a blueprint to disrupt the human dynein-LIS1 interactions more accurately and maps mutations linked to malformations of cortical development/intellectual disability and type-1 lissencephaly disease in the context of the dynein-LIS1 complex.
Article
Multidisciplinary Sciences
Xizi Chen, Xiaotong Yin, Jiabei Li, Zihan Wu, Yilun Qi, Xinxin Wang, Weida Liu, Yanhui Xu
Summary: This study investigates the mechanisms of TFIID and Mediator proteins in regulating transcription initiation and RNA polymerase activity, revealing their interactions and mutual regulation through structural analysis, as well as the phosphorylation process of Pol II CTD by CDK7.
Article
Multidisciplinary Sciences
Kirill D. Nadezhdin, Irina A. Talyzina, Aravind Parthasarathy, Arthur Neuberger, David X. Zhang, Alexander I. Sobolevsky
Summary: Nadezhdin et al. present structures of human TRPV4 in complex with the GTPase RhoA, revealing the mechanisms of channel activation, inhibition, and disease-causing mutations. TRPV4 is a polymodal cellular sensor involved in various physiological processes and diseases. The study demonstrates the interaction between TRPV4 and RhoA, identifies the binding sites of agonist 4α-PDD and inhibitor HC-067047, and provides insights into the activation and inhibition of TRPV4, laying the foundation for the development of therapeutics for TRPV4-related diseases.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Matthew J. Ryan, Lujia Gao, Francis I. Valiyaveetil, Martin T. Zanni, Alexei A. Kananenka
Summary: The potassium ion configurations in the selectivity filter of the KcsA ion channel protein were investigated using 2D IR spectroscopy. The study found that in the closed conductive state of the KcsA channel, K+ ions do not occupy adjacent binding sites. The experimental data supported the soft-knock ion configurations rather than the hard-knock ion configurations.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Cell Biology
Alessandro Bortolami, Federico Sesti
Summary: Ion channels modulate cellular excitability by regulating ionic fluxes across biological membranes. Pathogenic mutations in ion channel genes give rise to epileptic disorders that are among the most frequent neurological diseases affecting millions of individuals worldwide. Furthermore, certain alleles are associated with brain malformations even in the absence of a clear electrical phenotype. This body of evidence argues that the underlying epileptogenic mechanisms of ion channels are more diverse than originally thought.
NEURAL REGENERATION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Qixiang He, Xiuhua Lin, Bianca L. Chavez, Sourav Agrawal, Benjamin L. Lusk, Ci Ji Lim
Summary: This study reveals that the CST accessory protein helps organize the Pol alpha-primase enzyme for efficient primer synthesis. Cryogenic electron microscopy structures show that CST separates the DNA and RNA catalytic centers of Pol alpha-primase into two domains and arranges them in the correct order for RNA-DNA synthesis. The study also provides insights into the template-binding specificity of CST and its role in the assembly and activation of the CST-Pol alpha-primase complex.
Article
Biochemistry & Molecular Biology
Angelo Felline, Simone Conti, Michele Seeber, Marco Cecchini, Francesca Fanelli
Summary: This article presents the second update of Wordom, a program for manipulation and analysis of conformational ensembles from molecular simulations. The update expands existing modules and adds 21 new modules, which can be grouped into three sets analyzing atomic fluctuations and communication, ion-channel dynamics, and structural deformation. The updates enhance Wordom's suitability, completeness, user-friendliness, and efficiency for biomolecular simulation analysis.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Article
Multidisciplinary Sciences
Mingfeng Zhang, Yuanyue Shan, Duanqing Pei
Summary: Human Eag2 is a voltage-gated potassium channel that exhibits unique delayed rectifying gating kinetics. In this study, the authors elucidate the mechanism of how voltage opens the channel and sheds light on delayed rectifier gating. They use cryo-electron microscopy to capture multiple conformations of hEag2, revealing the dynamics of the selectivity filter and ion permeation pathway at the atomic level. The study also uncovers the involvement of the S4-S5 linker and an additional potassium ion in voltage transduction and the generation of delayed rectifier properties.
NATURE COMMUNICATIONS
(2023)
Article
Food Science & Technology
Lorenzo Pallante, Marta Malavolta, Gianvito Grasso, Aigli Korfiati, Seferina Mavroudi, Bojan Mavkov, Athanasios Kalogeras, Christos Alexakos, Vanessa Martos, Daria Amoroso, Giacomo di Benedetto, Dario Piga, Konstantinos Theofilatos, Marco A. Deriu
Summary: This review provides an overview of the molecular mechanisms involved in taste transduction, focusing on taste receptors and the activation/deactivation of specific cell signalling pathways. It also highlights the advances in molecular research and computational investigation of ligand-receptor interaction related to taste receptors, aiming to understand the transfer of taste information.
TRENDS IN FOOD SCIENCE & TECHNOLOGY
(2021)
Article
Biophysics
Yu Wang, Zhipu Luo, Xavier Morelli, Peng Xu, Longguang Jiang, Xiaoli Shi, Mingdong Huang
Summary: In this study, the direct binding of lysophospholipids (lysoPLs), specifically LPC, to human serum albumin (HSA) was demonstrated using fluorescence quenching and optical interferometry assays. The crystal structure analysis revealed the binding sites of LPC on HSA and showed that HSA can still bind to LPC in the presence of myristate. These findings provide insights into the role of HSA as a carrier protein for lysoPLs in blood plasma and the structural basis of their binding mechanisms.
BIOPHYSICAL JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Pedro Martin, Melisa Moncada, Karen Castillo, Federico Orsi, Geronimo Ducca, Jose Manuel Fernandez-Fernandez, Carlos Gonzalez, Veronica Milesi
Summary: Arachidonic acid (AA) directly activates BK channels co-expressed with the auxiliary beta 1 subunit, stabilizing the voltage sensor domain (VSD) on its active configuration and facilitating channel opening transitions when VSD are at rest and CSD are unoccupied. The activation is independent of intracellular Ca2+ concentration and reduced when co-expressed with the Y74A mutant of the beta 1 subunit.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2021)
Article
Multidisciplinary Sciences
Yingying Guo, Yuanyuan Zhang, Renhong Yan, Bangdong Huang, Fangfei Ye, Liushu Wu, Ximin Chi, Yi Shi, Qiang Zhou
Summary: This study reports the structures of human NKA, providing insights into the cytoplasmic Na+ entrance pathway and the mechanism of cytoplasmic gate closure coupled with ATP hydrolysis. This fills crucial gaps in understanding the working cycle of NKA.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Robert C. Monsen, Srinivas Chakravarthy, William L. Dean, Jonathan B. Chaires, John O. Trent
Summary: The study used an integrated structural biology approach to characterize the structure of telomeric overhang, revealing that single-stranded sequences fold into multimeric structures with a maximum number of G4 units. The flexibility of these structures was investigated through molecular dynamics simulations, identifying unique sites for drug targeting.
NUCLEIC ACIDS RESEARCH
(2021)