Article
Cell Biology
Xiaofei Wang, Yawen Li, Hong Wei, Zhisen Yang, Rui Luo, Yongxiang Gao, Wei Zhang, Xin Liu, Linfeng Sun
Summary: TRPA1 is an ion channel that responds to noxious temperature or chemical stimuli. The thermosensitivity of TRPA1 varies among different species or isoforms. This study determines the structures of a heat-sensitive isoform of TRPA1 in fruit flies and identifies conformational changes in the ankyrin repeat domain and coiled-coil domain. The findings provide insights into the gating mechanism of TRPA1.
Review
Biochemistry & Molecular Biology
Roberto Maglie, Daniel Souza Monteiro de Araujo, Emiliano Antiga, Pierangelo Geppetti, Romina Nassini, Francesco De Logu
Summary: TRPA1, a member of the TRP superfamily, plays a crucial role in sensory neurons and has been found to be expressed in various skin cells, contributing to skin physiology and pathophysiology. Recent studies have highlighted the potential use of TRPA1 antagonists in the treatment of inflammatory and immunological skin disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Thi Hong Dung Nguyen, Stella Chapman, Makiko Kashio, Claire Saito, Tatjana Strom, Mio Yasui, Makoto Tominaga
Summary: This study reveals the structural basis of mosquito thermosensitive TRPA1 protein, which helps to understand the determination of temperature threshold and the evolutionary adaptation of mosquito TRPA1 to different climates.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Zelin Hu, Ya Zhang, Wenhan Yu, Junjie Li, Jiaqi Yao, Jifa Zhang, Jiaxing Wang, Chengdi Wang
Summary: The TRPA1 channel is a non-selective cation channel that detects irritant chemicals and is associated with pain, inflammation, and pruritus. TRPA1 antagonists have shown promise as treatments for various diseases, but their performance in clinical studies has been disappointing. There is a need for antagonists with higher selectivity, metabolic stability, and solubility. Additionally, TRPA1 agonists help in understanding activation mechanisms and aid in the screening of antagonists. This perspective summarizes the recent development of TRPA1 antagonists and agonists, focusing on structure-activity relationships and pharmacological activity, with the aim of inspiring the development of more effective TRPA1-modulating drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Matthew Habgood, David Seiferth, Afroditi-Maria Zaki, Irfan Alibay, Philip C. Biggin
Summary: TRPA1 is a chemosensor that responds to a wide spectrum of irritants and sensations. This study uses molecular dynamics simulations to investigate the mechanism of electrophilic activation and stabilizing the open state of the ion channel TRPA1. The results suggest that binding of electrophiles at specific sites stabilizes the open state of the channel, and the rotation of molecules bound at one of the sites allows for immediate stabilization of transient open states.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Yawen Li, Yinan Ding, Lili Qu, Xinru Li, Qinxuan Lai, Pingxia Zhao, Yongxiang Gao, Chengbin Xiang, Chunlei Cang, Xin Liu, Linfeng Sun
Summary: Stomata are crucial for gas exchange and photosynthesis regulation in plants. The anion channel SLAC1 plays a central role in stomatal closure upon phosphoactivation. Through structural analysis and electrophysiology, an inhibition-release model is proposed where phosphorylation triggers dissociation of a cytosolic plug from SLAC1 transmembrane domains to induce conformational changes in the pore-forming helices.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Diana Avalos, Guillaume Rey, Diogo M. Ribeiro, Anna Ramisch, Emmanouil T. Dermitzakis, Olivier Delaneau
Summary: An analysis of cis-regulatory domains (CRDs) derived from ChIP-seq peaks and methylation data reveals cell-type specific regulatory mechanisms in immunity. Important biological mechanisms, such as cell-specific transcription factor binding sites and immune disease-associated loci, are discovered through this study. CRD-QTLs aid in interpreting GWAS findings and mapping functional regulatory units using population genomics allows the discovery of important mechanisms in gene expression regulation in immune cells. This study establishes a comprehensive resource for understanding cell-type specific regulatory mechanisms of immunity.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Lavanya Moparthi, Viktor Sinica, Vamsi K. Moparthi, Mohamed Kreir, Thibaut Vignane, Milos R. Filipovic, Viktorie Vlachova, Peter M. Zygmunt
Summary: The temperature gating of hTRPA1 is regulated by the N-ARD and VSLD domains. The CTD is involved in cold sensitivity, while the VSLD is involved in heat sensitivity, and they are allosterically coupled to the channel pore gating.
NATURE COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Louis Tung Faat Lai, Jayashree Balaraman, Fei Zhou, Doreen Matthies
Summary: Magnesium ions (Mg2+) are crucial for cellular physiology, and MRS2 is a channel responsible for regulating Mg2+ influx and homeostasis in mitochondria. This study provides insights into the gating residues and Mg2+ binding sites of MRS2, shedding light on the translocation and regulatory mechanisms of Mg2+.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Avnika Bali, Samantha P. Schaefer, Isabelle Trier, Alice L. Zhang, Lilian Kabeche, Candice E. Paulsen
Summary: In this study, a TRPA1 gene mutation (R919*) identified in CRAMPT syndrome patients was found to confer hyperactivity when co-expressed with wild type TRPA1. The mutant and wild type subunits co-assembled into functional heteromeric channels, which enhanced agonist sensitivity and calcium permeability, explaining the observed symptoms. The findings expand our understanding of the physiological impact of nonsense mutations, provide insights into TRPA1 gating, and motivate genetic analysis of pain syndromes.
NATURE COMMUNICATIONS
(2023)
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)
Article
Multidisciplinary Sciences
A. Catalina Velez-Ortega, Ruben Stepanyan, Stephanie E. Edelmann, Sara Torres-Gallego, Channy Park, Desislava A. Marinkova, Joshua S. Nowacki, Ghanshyam P. Sinha, Gregory I. Frolenkov
Summary: TRPA1 channels are expressed in nociceptive neurons and in the cochlea, and their function in the cochlea is unknown. This study shows that TRPA1 activation in the supporting cells of the cochlea causes prolonged calcium responses, leading to contractions of pillar and Deiters' cells. TRPA1 channels are activated by oxidative stress and extracellular ATP, which are present after acoustic trauma. TRPA1 deficiency results in larger but less prolonged temporary shift in hearing thresholds, indicating its contribution to cochlear sensitivity regulation after noise exposure.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Nannan Su, Wenxuan Zhen, Heng Zhang, Lingyi Xu, Yitian Jin, Xiaoying Chen, Cheng Zhao, Qinrui Wang, Xinyan Wang, Shaowei Li, Han Wen, Wei Yang, Jiangtao Guo, Fan Yang
Summary: This study reports the presence of an endogenous cholesterol molecule inside the TRPV2 receptor, which antagonizes ligand activation and is removed by methyl-beta-cyclodextrin. Additionally, the study shows that estradiol can enhance TRPV2 activation. These findings provide a structural basis for understanding the regulation of TRPV2.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Qiushuang Ji, Sai Shi, Biao Ma, Weiwei Zhang, Hailong An, Shuai Guo
Summary: A study found that candesartan (CDST), an angiotensin converting enzyme inhibitor, can effectively inhibit the activity of the TMEM16A channel and has inhibitory effects on the proliferation, migration, and apoptosis of lung adenocarcinoma cells, showing promising anti-lung adenocarcinoma activity. Considering that CDST has been used in clinical treatment of hypertension, it may play an important role as a multi-target drug in the future combined treatment of hypertension and lung adenocarcinoma.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Review
Biochemistry & Molecular Biology
Houria Daimi, Estefania Lozano-Velasco, Amelia Aranega, Diego Franco
Summary: This review provides the latest information on the molecular events that regulate the Na(v)1.5 sodium channel and the cardiac channelopathies associated with defects in these pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
