Article
Multidisciplinary Sciences
Qiurong Wu, Jian Huang, Xiao Fan, Kan Wang, Xueqin Jin, Gaoxingyu Huang, Jiaao Li, Xiaojing Pan, Nieng Yan
Summary: This article reports the high-resolution cryo-EM structures of human Na(v)1.7 bound to drugs and lead compounds, revealing the binding mode of these compounds on Na-v channels. The study demonstrates that different drugs can bind to different locations on the channel, providing a 3D structural map of known drug-binding sites.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Goragot Wisedchaisri, Lige Tonggu, Tamer M. Gamal El-Din, Eedann McCord, Ning Zheng, William A. Catterall
Summary: This research engineered a model sodium channel to determine the structure of the channel functionally arrested by spider toxin, revealing a high-affinity interaction mechanism between the toxin and the channel. This provides guidance for developing future resting-state-targeted analgesic drugs.
Article
Biology
Kangcheng Song, Miao Wei, Wenjun Guo, Li Quan, Yunlu Kang, Jing-Xiang Wu, Lei Chen
Summary: TRPC5 channel is a nonselective cation channel involved in various physiological processes. Inhibitors of TRPC5, such as clemizole and HC-070, stabilize the ion channel in a nonconductive closed state, potentially offering new therapeutic strategies for anxiety disorders, depression, and kidney diseases. The cryo-EM structures of human TRPC5 with inhibitors provide insights into the binding sites and inhibitory mechanisms, facilitating the development of more effective inhibitors targeting TRPC5.
Article
Multidisciplinary Sciences
Emma C. Couves, Scott Gardner, Tomas B. Voisin, Jasmine K. Bickel, Phillip J. Stansfeld, Edward W. Tate, Doryen Bubeck
Summary: This study reveals the role of CD59 in immune regulation, by preventing the formation of MAC toxins through inhibiting the binding of C8 and C9 to the membrane. CD59 also protects membrane integrity by altering the trajectory of C9 beta-hairpins, restricting MAC polymerization. These findings are significant for understanding the dual roles of CD59 in MAC and its involvement in host-pathogen interactions.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Gabriele A. Trombetti, Alessandra Mezzelani, Alessandro Orro
Summary: Chronic pain is a common disorder that is inadequately addressed by current analgesics. Inhibition of the voltage-gated sodium channel Nav1.7 has been proposed as a promising approach to completely cancel pain perception. However, the lack of selective Nav1.7 inhibitors poses a challenge in drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shuai Gao, Xia Yao, Jiaofeng Chen, Gaoxingyu Huang, Xiao Fan, Lingfeng Xue, Zhangqiang Li, Tong Wu, Yupeng Zheng, Jian Huang, Xueqin Jin, Yan Wang, Zhifei Wang, Yong Yu, Lei Liu, Xiaojing Pan, Chen Song, Nieng Yan
Summary: Cav1.2 channels have important functions in neuronal and physiological processes. Cryo-EM structures of human Cav1.2 in different states, including its apo form and in complex with drugs or peptides, reveal consistent inactivated conformations. The binding of certain drugs induces structural changes, such as upward movement of VSDII and dilation of the selectivity filter and its surrounding segments.
Article
Multidisciplinary Sciences
Shabareesh Pidathala, Aditya Kumar Mallela, Deepthi Joseph, Aravind Penmatsa
Summary: The researchers used the Drosophila melanogaster dopamine transporter as a surrogate to study the structure and function of norepinephrine, revealing potential paradigms for designing chronic pain inhibitors.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
He-ling Niu, Ya-ni Liu, Deng-qi Xue, Li-ying Dong, Hui-jie Liu, Jing Wang, Yi-lin Zheng, An-ruo Zou, Li-ming Shao, KeWei Wang
Summary: QLS-81, a novel Nav1.7 channel inhibitor, demonstrated efficacy in alleviating chronic pain in mice, indicating potential for pain therapy.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Multidisciplinary Sciences
Goragot Wisedchaisri, Tamer M. Gamal El-Din, Ning Zheng, William A. Catterall
Summary: Gain-of-function mutations in the voltage-gated sodium channel NaV1.7, specifically in the S4-S5 intracellular linker, lead to severe inherited pain syndromes. Through structural analysis, it has been discovered that these mutations create new hydrogen bonds, stabilizing the activated state of the channel and causing a negative shift in voltage dependence of activation. This study provides important insights into the mechanisms behind hyperexcitability of NaV1.7 and severe pain in inherited erythromelalgia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Qin Gong, Kim Robinson, Chenrui Xu, Phuong Thao Huynh, Kelvin Han Chung Chong, Eddie Yong Jun Tan, Jiawen Zhang, Zhao Zhi Boo, Daniel Eng Thiam Teo, Kenneth Lay, Yaming Zhang, John Soon Yew Lim, Wah Ing Goh, Graham Wright, Franklin L. Zhong, Bruno Reversade, Bin Wu
Summary: NLRP1 and CARD8 are two recently characterized sensor proteins for the human inflammasome complex. The cryo-EM CARD filament structures of the NLRP1 and CARD8 activating domains reveal how NLRP1 and CARD8 discriminate between ASC and pro-caspase-1. The authors propose a two-step model for NLRP1 activation.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Inorganic & Nuclear
Hong Cai, Jie-Wen Wu, Xiao-Jun Cai, Zhou Lu, Ya-Liang Lai, Jing-Xuan Sun, Zhuo-Li Yuan, Yang-Ying Huang, Jing-Wen Cai, Wen Lu, Yi-Hong Lu, Hui-Ying Zhang, Dan Li
Summary: By combining supramolecular chemistry and bioscience, a novel purine-based MOF, HSTC-1, with chiral helical channels has been successfully constructed, which can identify H2O2 through a fluorescence quenching effect. The adsorption of H2O2 molecules through the chiral channels induces chiral distribution of subsequent guests to form a host-guest recognition system of H2O2@HSTC-1, slowing down the oxidation of the host framework. This work provides unique insights for constructing intelligent protection matrix materials and has significant implications in pharmacochemistry and biomedicine.
INORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Multidisciplinary Sciences
Rong Wang, Jin Wang, Abdirahman Hassan, Chia-Hsueh Lee, Xiao-Song Xie, Xiaochun Li
Summary: The study reveals the structural basis for Bafilomycin A1 inhibition of V-ATPase, showing that six Bafilomycin A1 molecules bind to the c-ring and disrupt the interactions between the c-ring and subunit a, thus preventing proton translocation.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Jialiang Wang, Jingdan Liang, Lu Chen, Wei Zhang, Liangliang Kong, Chao Peng, Chen Su, Yi Tang, Zixin Deng, Zhijun Wang
Summary: Statins, effective cholesterol-lowering drugs, depend on a megasynthase complex for biosynthesis. CryoEM structures of LovB-LovC and core LovB provide insights into the catalytic cycle for lovastatin production.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Minjee Kwon, Il Young Jung, Myeounghoon Cha, Bae Hwan Lee
Summary: Pulpitis causes changes in the peripheral nervous system, leading to hyperalgesia. Experimental pulpitis activates Nav1.7 expression peripherally and affects TG neuronal activity. Inhibition of the Nav1.7 channel can modulate nociceptive signal processing in the TG following pulp inflammation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Menghang Huang, Xiaoxiao Zhang, Gee Ann Toh, Qin Gong, Jia Wang, Zhifu Han, Bin Wu, Franklin Zhong, Jijie Chai
Summary: The study demonstrates that full-length rat NLRP1 and rat DPP9 can form a complex to suppress NLRP1 activation. The ZU5 domain is essential for both autoinhibition of NLRP1 and assembly of the complex. Furthermore, both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells.
Article
Multidisciplinary Sciences
Wen-Ying Liu, Jiang-Tao Zhang, Takuya Miyakawa, Guo-Ming Li, Rui-Zeng Gu, Masaru Tanokura
Summary: This study identified potent antioxidant peptides and ACE inhibitory peptides from wheat gluten oligopeptides (WOP), which could potentially be applied in the food industry as a functional additive. Novel antioxidative/ACE inhibitory peptides were discovered, suggesting a promising high-value utilization of raw wheat gluten.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Daohua Jiang, Richard Banh, Tamer M. Gamal El-Din, Lige Tonggu, Michael J. Lenaeus, Regis Pomes, Ning Zheng, William A. Catterall
Summary: Research has uncovered the open-state structure of the sodium channel Na(v)1.5, revealing the mechanism of pore opening by blocking fast inactivation. This provides crucial molecular-level insights into the initiation of heartbeat.
Article
Food Science & Technology
Ruixue Zhang, Ying Wei, Jiangtao Zhang, Muyi Cai, Lu Lu, Lei Fang, Xiuyuan Qin, Ruizeng Gu
Summary: The study demonstrated the beneficial effects of rice protein hydrolysate (RPH) and its characteristic peptides on UVB-induced photodamage in guinea pigs. RPH improved antioxidant capacity, prevented water and collagen loss, and protected skin tissue by regulating signaling pathways. LPK and pEK were identified as key peptides in promoting collagen expression.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Cell Biology
Yanli Dong, Yiwei Gao, Shuai Xu, Yuhang Wang, Zhuoya Yu, Yue Li, Bin Li, Tian Yuan, Bei Yang, Xuejun Cai Zhang, Daohua Jiang, Zhuo Huang, Yan Zhao
Summary: This study sheds light on the structure of the human Ca(V)2.2 channel complex, providing insights for developing new state-dependent blockers for the treatment of chronic pain.
Article
Multidisciplinary Sciences
Jiangtao Zhang, Yiqiang Shi, Junping Fan, Huiwen Chen, Zhanyi Xia, Bo Huang, Juquan Jiang, Jianke Gong, Zhuo Huang, Daohua Jiang
Summary: This study reveals a novel mechanism for fast inactivation of voltage-gated sodium channels in Emiliania huxleyi, which is independent of the conventional Ile-Phe-Met motif. A N-terminal helix of Na(V)Eh blocks the activation gate to achieve fast inactivation. This mechanism enables rapid inactivation but delayed recovery compared to human Na-V channels.
NATURE COMMUNICATIONS
(2022)
Review
Pharmacology & Pharmacy
Daohua Jiang, Jiangtao Zhang, Zhanyi Xia
Summary: Voltage-gated sodium channels are crucial for the rapid rising-phase of action potentials, and their mutations can lead to various human diseases. Recent studies using cryo-EM structures have provided valuable insights into the mechanism of eukaryotic Na-V channels, offering templates for drug development.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Junping Fan, Linghan Hu, Zongwei Yue, Daohong Liao, Fusheng Guo, Han Ke, Daohua Jiang, Yong Yang, Xiaoguang Lei
Summary: The TRPV3 channel has important roles in skin physiology. Trpvicin, identified in this study, is a potent and subtype-selective inhibitor of TRPV3, which shows pharmacological potential in the inhibition of itch and hair loss. The research provides mechanistic insights into the inhibition of TRPV3 by Trpvicin and supports drug development targeting TRPV3.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Food Science & Technology
Ruixue Zhang, Jiangtao Zhang, Yan Liu, Lei Fang, Ying Wei, Ruizeng Gu, Min Lin, Liang Chen, Zhengfu Zhou
Summary: Supplementation of FWPH improves anti-fatigue ability, enhances exercise performance, and alters intestinal flora composition.
JOURNAL OF FUNCTIONAL FOODS
(2022)
Article
Multidisciplinary Sciences
Sina Jami, Jennifer R. Deuis, Tabea Klasfauseweh, Xiaoyang Cheng, Sergey Kurdyukov, Felicity Chung, Andrei L. Okorokov, Shengnan Li, Jiangtao Zhang, Ben Cristofori-Armstrong, Mathilde R. Israel, Robert J. Ju, Samuel D. Robinson, Peng Zhao, Lotten Ragnarsson, Asa Andersson, Poanna Tran, Vanessa Schendel, Kirsten L. McMahon, Hue N. T. Tran, Yanni K. -Y. Chin, Yifei Zhu, Junyu Liu, Theo Crawford, Saipriyaa Purushothamvasan, Abdella M. Habib, David A. Andersson, Lachlan D. Rash, John N. Wood, Jing Zhao, Samantha J. Stehbens, Mehdi Mobli, Andreas Leffler, Daohua Jiang, James J. Cox, Stephen G. Waxman, Sulayman D. Dib-Hajj, G. Gregory Neely, Thomas Durek, Irina Vetter
Summary: This study demonstrates the essential role of TMEM233 in the activity of stinging nettle toxins and its modulation of gating properties of Na(V)1.7. These findings identify TMEM233 as an interacting protein of Na(V)1.7, position TMEM233 and dispanins as indispensable accessory proteins for toxin-mediated effects on Na-V channel gating, and provide important insights into the function of Na-V channels in sensory neurons.
NATURE COMMUNICATIONS
(2023)
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
Multidisciplinary Sciences
Sina Jami, Jennifer R. Deuis, Tabea Klasfauseweh, Xiaoyang Cheng, Sergey Kurdyukov, Felicity Chung, Andrei L. Okorokov, Shengnan Li, Jiangtao Zhang, Ben Cristofori-Armstrong, Mathilde R. Israel, Robert J. Ju, Samuel D. Robinson, Peng Zhao, Lotten Ragnarsson, Asa Andersson, Poanna Tran, Vanessa Schendel, Kirsten L. McMahon, Hue N. T. Tran, Yanni K. -Y. Chin, Yifei Zhu, Junyu Liu, Theo Crawford, Saipriyaa Purushothamvasan, Abdella M. Habib, David A. Andersson, Lachlan D. Rash, John N. Wood, Jing Zhao, Samantha J. Stehbens, Mehdi Mobli, Andreas Leffler, Daohua Jiang, James J. Cox, Stephen G. Waxman, Sulayman D. Dib-Hajj, G. Gregory Neely, Thomas Durek, Irina Vetter
Summary: TMEM233 protein is essential for the activity of ExTxA toxin on Na-V channels, and co-expression of TMEM233 modulates the gating properties of Na(V)1.7.
NATURE COMMUNICATIONS
(2023)