Article
Neurosciences
Maria Antonietta Coppola, Paola Gavazzo, Ilaria Zanardi, Abraham Tettey-Matey, Antonella Liantonio, Peying Fong, Michael Pusch
Summary: ClC-6 and ClC-7 are closely related intracellular Cl-/H+ antiporters that belong to the CLC family of channels and transporters. They play important roles in regulating ionic homeostasis in late endosomes and lysosomes. While the transport function of ClC-7 requires the association with the accessory protein Ostm1, ClC-6 does not. By studying their Cl- and pH-dependence, researchers have discovered unique characteristics and functional nuances of these proteins, as well as disease-associated mutants. The findings highlight the distinct roles of ClC-6 and ClC-7 in the context of their localization, and provide insights into the mechanisms underlying diseases associated with these proteins.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Chemistry, Medicinal
Davide Sala, Andrea Giachetti, Antonio Rosato
Summary: ZnT8, a human zinc transporter, shows significant differences in zinc ion transport kinetics and conformational dynamics between different variants, which may lead to different disease risks.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Amanat Ali, Elizabeth K. M. Johnstone, Bincy Baby, Heng B. See, Angela Song, K. Johan Rosengren, Kevin D. G. Pfleger, Mohammed Akli Ayoub, Ranjit Vijayan
Summary: The study demonstrated the allosteric effect of LVV-H7 on AngII binding, showing that LVV-H7 can enhance the binding of AngII to AT1R through an allosteric mechanism, supporting the pharmacological targeting of AT1R by hemorphins for potential implications in vascular and renal physiology.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Jordane Preto, Hubert Gorny, Isabelle Krimm
Summary: In this study, we used accelerated molecular dynamics simulations to investigate the closed states of VDAC1. Our results suggest that the low-conducting states of VDAC1 are primarily caused by the positioning of an unfolded part of the N-terminus, rather than a displacement of the voltage sensor or a significant change in the pore. Our findings are consistent with experimental evidence and support the idea that entropy plays a key role in VDAC gating.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Giovanni Zifarelli
Summary: CLC proteins, including Cl- channels and anion/H+ antiporters, play critical roles in various physiological processes. ClC-7, as a lysosomal Cl-/H+ antiporter, is crucial for the ionic homeostasis in lysosomes and osteoclasts' resorption lacuna. Mutations in ClC-7 can lead to osteopetrosis, lysosomal storage disease, and neurodegeneration.
Article
Biochemistry & Molecular Biology
Gaurika Garg, Christian Dienemann, Lucas Farnung, Juliane Schwarz, Andreas Linden, Henning Urlaub, Patrick Cramer
Summary: We provide mechanistic insights into the three major steps of human co-transcriptional pre-mRNA capping based on six different cryo-EM structures. The human mRNA capping enzyme, RNGTT, first docks to the Pol II stalk to position its triphosphatase domain near the RNA exit site. The capping enzyme then moves onto the Pol II surface, and its guanylyltransferase receives the pre-mRNA 5'-diphosphate end.
Article
Chemistry, Physical
Fatemeh Yazdani, Behzad Shareghi, Sadegh Farhadian, Lida Momeni
Summary: This study investigated the effects of naringenin on the structure of human serum albumin (HSA) using spectroscopic and computational methods. The results showed that naringenin can bind to HSA, increasing its stability and reducing its flexibility.
JOURNAL OF MOLECULAR LIQUIDS
(2022)
Review
Plant Sciences
Neha Handa, Pawan Gupta, Kanika Khanna, Sukhmeen Kaur Kohli, Renu Bhardwaj, Pravej Alam, Parvaiz Ahmad
Summary: Metalloids play diverse physiological roles in plants, influencing crop yield and quality. Aquaporins, a group of membrane channels, have been found to have a significant role in regulating plant metalloid homeostasis. More research is needed to unravel the mechanisms of metalloid trafficking and the future applications of aquaporins in plant growth and development.
PHYSIOLOGIA PLANTARUM
(2022)
Article
Chemistry, Medicinal
Liang Xu, Clyde F. Phelix, Liao Y. Chen
Summary: This study developed de novo models of human MPC complexes and characterized the conformational dynamics of the MPC1/2 heterodimer. It was found that functional MPC1/2 tends to adopt an inward-open conformation and can regulate pyruvate transport by stably binding to substrate or inhibitor.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2021)
Article
Biochemistry & Molecular Biology
Eleni Papakonstantinou, Dimitrios Vlachakis, Trias Thireou, Panayiotis G. Vlachoyiannopoulos, Elias Eliopoulos
Summary: MCTs are being researched for their role in cancer cell metabolism and ability to transport drugs across the membrane. Differences among MCTs lie in their specific metabolic roles, substrate and inhibitor affinities, expression regulation, intracellular localization, and tissue distribution. MCT4 is essential for maintaining the glycolytic phenotype of cancer cells and promoting extracellular acidification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Environmental Sciences
Huihui Zhang, Nengde Zeng, Qiurun Feng, Shuangyuan Xu, Jian Cheng, Jiawei Wang, Xinhua Zhan
Summary: Polycyclic aromatic hydrocarbons (PAHs), highly carcinogenic organic pollutants, are actively taken up by plant roots through H+/PAHs co-transport. The involvement of ABC transporters in PAHs co-transport was investigated using phenanthrene-exposed wheat roots. Up-regulated or newly expressed ABC transporters with alkalinity and hydrophobicity were identified, and their expression was positively correlated with phenanthrene concentration. Docking simulations revealed stable binding between ABC transporters and PAHs, with pi-pi stacking and van der Waals force playing crucial roles. These findings contribute to our understanding of how ABC transporters aid plant root uptake of PAHs.
SCIENCE OF THE TOTAL ENVIRONMENT
(2023)
Review
Pharmacology & Pharmacy
David Machalz, Szymon Pach, Marcel Bermudez, Matthias Bureik, Gerhard Wolber
Summary: This review summarizes recent structural insights into understudied cytochrome P450 enzymes, highlighting the impact of molecular modeling for mechanistically explaining pathophysiological effects and establishing understudied CYPs as promising drug targets.
DRUG DISCOVERY TODAY
(2021)
Article
Biochemistry & Molecular Biology
Osmair Vital de Oliveira, Arlan da Silva Goncalves, Natalia Ellen Castilho de Almeida
Summary: In this study, molecular dynamic simulations were conducted to investigate the prevention of A beta(1-42) aggregation by CB[7]. The results show that CB[7] disrupts the stability of salt bridge and exerts steric effects to prevent the elongation of A beta(1-42) fibrils.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Biochemistry & Molecular Biology
Osmair Vital de Oliveira, Arlan da Silva Goncalves, Natalia Ellen Castilho de Almeida
Summary: The study revealed that CB[7] prevents the elongation of Aβ(1-42) protofibrils by disrupting the Asp23-Lys28 salt bridge and through steric effects, rather than through the transition from alpha-helix to beta-sheet as previously proposed.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2021)
Article
Cell Biology
Jie Yu, Bing Zhang, Yixiao Zhang, Cong-qiao Xu, Wei Zhuo, Jingpeng Ge, Jun Li, Ning Gao, Yang Li, Maojun Yang
Article
Multidisciplinary Sciences
Jinke Gu, Laixing Zhang, Shuai Zong, Runyu Guo, Tianya Liu, Jingbo Yi, Peiyi Wang, Wei Zhuo, Maojun Yang
Letter
Cell Biology
Wei Zhuo, Heng Zhou, Runyu Guo, Jingbo Yi, Laixing Zhang, Lei Yu, Yinqiang Sui, Wenwen Zeng, Peiyi Wang, Maojun Yang
Article
Cell Biology
Wenhe Wang, Xudong Chen, Laixing Zhang, Jingbo Yi, Qingxi Ma, Jian Yin, Wei Zhuo, Jinke Gu, Maojun Yang
Article
Biology
Sensen Zhang, Jun Zhou, Yuebin Zhang, Tianya Liu, Perrine Friedel, Wei Zhuo, Suma Somasekharan, Kasturi Roy, Laixing Zhang, Yang Liu, Xianbin Meng, Haiteng Deng, Wenwen Zeng, Guohui Li, Biff Forbush, Maojun Yang
Summary: In this study, the cryo-electron microscopy structures of the two neuronal cation-chloride cotransporters human NKCC1 and mouse KCC2 were presented, identifying essential residues for ion transport. The study proposes mechanisms by which phosphorylation regulates the activity of these cation-chloride cotransporters.
COMMUNICATIONS BIOLOGY
(2021)
Article
Cell Biology
Sensen Zhang, Baolei Yuan, Jordy Homing Lam, Jun Zhou, Xuan Zhou, Gerardo Ramos-Mandujano, Xueyuan Tian, Yang Liu, Renmin Han, Yu Li, Xin Gao, Mo Li, Maojun Yang
Summary: The expression of PANX1 is upregulated by various stimuli in human macrophages that promote pyroptosis, with structural and functional studies revealing its potential role in pyroptosis during immune responses. Cryo-electron microscopy and molecular dynamics simulations support the model of hPANX1 as a homo-heptamer with N-termini and C-termini extending deep into the channel pore funnel, providing insights into the channel gating mechanism.
Article
Biochemistry & Molecular Biology
Jinke Gu, Tianya Liu, Runyu Guo, Laixing Zhang, Maojun Yang
Summary: Cryo-EM structures of the porcine respiratory complex I reveal the binding and reduction mechanism of Q10 in the Q chamber. The study proposes a 'two-Q' model for the coupling mechanism of complex I. The findings overturn the widely accepted previous proposal and provide new insights into the structure and function of complex I.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2022)
Article
Cell Biology
Xudong Chen, Mingze Zhou, Sensen Zhang, Jian Yin, Ping Zhang, Xujun Xuan, Peiyi Wang, Zhiqiang Liu, Boda Zhou, Maojun Yang
Summary: The cryo-EM structures of three distinct intermediates of human ATP13A2 were reported, providing insights into the spermine transport cycle in the lysosome. The transmembrane domain serves as a substrate binding site, and the C-terminal domain is essential for protein stability. These findings advance understanding of the polyamine transport mechanism and associated disease mutants of ATP13A2.
Article
Biochemistry & Molecular Biology
Minghui Zhang, Laixing Zhang, Runyu Guo, Chun Xiao, Jian Yin, Sensen Zhang, Maojun Yang
Summary: In this study, the cryoelectron microscopy structures of the human LACTB (hLACTB) were determined. It was found that the assembly of hLACTB filaments requires three interfaces and the formation of higher order helical structures facilitates its cleavage activity. Furthermore, the study showed that the middle region is necessary for substrate hydrolysis but not for filament formation. The inhibitor-bound structure suggests that hLACTB may cleave peptide bonds adjacent to aspartic acid residues.
Article
Plant Sciences
Ming Chen, Annemarie Perez-Boerema, Laixing Zhang, Yanxue Li, Maojun Yang, Shizhong Li, Alexey Amunts