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
Lei Tan, Xiaolong Qi, Weining Kong, Jiachuan Jin, Dan Lu, Xu Zhang, Yue Wang, Siting Wang, Wei Dong, Xudong Shi, Wei Chen, Jianying Wang, Keru Li, Yuan Xie, Lijuan Gao, Feifei Guan, Kai Gao, Chaojun Li, Cheng Wang, Zhibin Hu, Lianfeng Zhang, Xuejiang Guo, Bin Shen, Yuanwu Ma
Summary: We used a modified DddA-derived cytosine base editor to introduce premature stop codons in mitochondrial protein-coding genes, resulting in the depletion of mtProteins in both cell and rat resources. This provides valuable tools for studying mtProtein-coding genes and developing therapeutic strategies.
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
Cell Biology
Peiyu Xu, Sijie Huang, Brian E. Krumm, Youwen Zhuang, Chunyou Mao, Yumu Zhang, Yue Wang, Xi-Ping Huang, Yong-Feng Liu, Xinheng He, Huadong Li, Wanchao Yin, Yi Jiang, Yan Zhang, Bryan L. Roth, H. Eric Xu
Summary: The dopaminergic system and its receptors (D1R to D5R) have important roles in the central nervous system. This study presents cryo-EM structures of all five subtypes of human dopamine receptors complexed with G protein and the pan-agonist rotigotine. The structures provide insight into rotigotine recognition, ligand polypharmacology, receptor activation, unique receptor subtype features, and G protein coupling specificity. This work offers a comprehensive set of structural templates for the development of specific ligands to target dopaminergic system-related CNS diseases.
Article
Biochemistry & Molecular Biology
Yang Xiao, Lianggui Xiao, Mingming Li, Songsong Liu, Yuwei Wang, Liang Huang, Siqi Liu, Tianyu Jiang, Lei Zhou, Yixing Li
Summary: Metabolic associated fatty liver disease is a major cause of chronic liver disease worldwide. In this study, we found that perillartine derived from Perilla frutescens (L.) improved fat deposition and glucose homeostasis in hepatocytes. In vitro, perillartine reduced lipid synthesis and transport, and increased mitochondrial content in hepatocytes. In vivo, perillartine reduced body weight gain, improved glucose metabolism, and altered gut microbial composition in mice fed a high-fat diet. Perillartine was also identified as a potential inhibitor for ROR gamma, a transcriptional activator involved in lipid accumulation and glucose metabolism. These findings suggest that perillartine could be a new candidate for the treatment of obesity and metabolic associated fatty liver disease.
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
Chemistry, Organic
Francisco Cen-Pacheco, Adrian J. Santiago-Benitez, Ka Yi Tsui, Dean J. Tantillo, Jose J. Fernandez, Antonio Hernandez Daranas
Summary: Six novel oxasqualenoids were isolated from the red alga Laurencia viridis, including compounds with unreported structural features and biogenetically intriguing properties. Quantum mechanical calculations were used to confirm their structures and explain key steps in the proposed biogenetic mechanisms for the formation of oxasqualenoids.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biology
Amit K. Gandhi, Zhen-Yu J. Sun, Walter M. Kim, Yu-Hwa Huang, Yasuyuki Kondo, Daniel A. Bonsor, Eric J. Sundberg, Gerhard Wagner, Vijay K. Kuchroo, Gregory A. Petsko, Richard S. Blumberg
Summary: Investigating the transitions of hCEACAM1 between monomeric and dimeric states is crucial for understanding its activity. By mutating residues within the hCEACAM1 IgV GFCC face and using various techniques, the study reveals the structural information and conformational behavior of hCEACAM1 in solution, highlighting the importance of the flexibility of the GFCC' face in governing the formation of hCEACAM1 dimers and selective heterodimers.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Jessica Joshua, Jeff Caswell, M. Lynne O'Sullivan, Geoffrey Wood, Sonja Fonfara
Summary: Hypertrophic cardiomyopathy (HCM) is the most common heart disease in cats, characterized by left ventricular hypertrophy. It is suggested as a translational animal model for the human disease. This study identified distinct gene expression patterns and pathways associated with HCM in cats, which are related to cardiac remodeling and fibrosis, inflammation, microvascular changes, calcium signaling, and cardiac metabolism.
Article
Biochemistry & Molecular Biology
Ming Guo, Yankun Duan, Shuyan Dai, Jun Li, Xiaojuan Chen, Lingzhi Qu, Zhuchu Chen, Hudie Wei, Longying Jiang, Yongheng Chen
Summary: The study found that Ponatinib inhibited wild type SRC kinase but failed to inhibit SRC gatekeeper mutants. By analyzing the crystal structure, the researchers provided a possible explanation for the different effects of Ponatinib on SRC and other kinases with gatekeeper mutations.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
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
Multidisciplinary Sciences
Charlotte Vajhoj, Benjamin Schmid, Ania Alik, Ronald Melki, Karina Fog, Bjorn Holst, Tina Charlotte Stummann
Summary: In this study, a humanized model was established with reproducibility and throughput to support target identification and validation in pharmacological research. By triggering intracellular alpha-synuclein aggregation through exposure to exogenously added fibrils, the model's scalability and suitability for detecting both increased and decreased aggregation were demonstrated. Gene modulation using siRNAs was also shown to be feasible, making the model suitable for genetic screening for modulators of alpha-synuclein aggregation.
Article
Biochemistry & Molecular Biology
Mohammad Mahmoudi Gomari, Parastoo Tarighi, Edris Choupani, Shadi Abkhiz, Masoud Mohamadzadeh, Neda Rostami, Esmaeil Sadroddiny, Soukayna Baammi, Vladimir N. Uversky, Nikolay V. Dokholyan
Summary: One of the main obstacles in prevention and treatment of COVID-19 is the rapid evolution of the SARS-CoV-2 Spike protein, which can affect the effectiveness of treatments. The B.1.617.2 lineage of SARS-CoV-2, characterized by many Spike mutations, shows high infectivity and resistance to current treatments.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)
Article
Mechanics
Ioannis Petromichelakis, Ioannis A. Kougioumtzoglou
Summary: A computational algebraic geometry technique is developed to determine nonlinear normal modes of multi-degree-of-freedom nonlinear dynamic systems, showing precise determination of solution sets of nonlinear algebraic systems and increased confidence in approximating NNMs using higher-order expansions. The technique's efficacy and potential are demonstrated through various numerical examples, and it can potentially be used with alternative definitions of NNMs and problem formulations requiring the solution of polynomial nonlinear algebraic equations.
INTERNATIONAL JOURNAL OF NON-LINEAR MECHANICS
(2021)
Article
Multidisciplinary Sciences
Xiang Zhang, Taolin Yuan, Jaap Keijer, Vincent C. J. de Boer
Summary: Seahorse XF analyzer is commonly used to measure mitochondrial OCR, but its complex data structure has not been adequately addressed in statistical analysis, impacting the robustness of statistical inference. OCRbayes, a Bayesian hierarchical modeling framework, has been developed to rigorously incorporate the complex data structure, showing potential for diagnosing patients with mitochondrial diseases.
Article
Biotechnology & Applied Microbiology
Quanfang Hu, Jingfang Wang, Zujiao Fu, Xiangtao Mo, Xuezhi Ding, Liqiu Xia, Youming Zhang, Yunjun Sun
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2015)
Article
Biochemical Research Methods
Lina Yang, Jingfang Wang, Jianfang Li, Hainan Zhang, Shujuan Guo, Min Yan, Zhenggang Zhu, Bin Lan, Youcheng Ding, Ming Xu, Wei Li, Xiaonian Gu, Chong Qi, Heng Zhu, Zhifeng Shao, Bingya Liu, Sheng-Ce Tao
MOLECULAR & CELLULAR PROTEOMICS
(2016)
Article
Biochemistry & Molecular Biology
Botao Fa, Shan Cong, Jingfang Wang
Article
Multidisciplinary Sciences
Hai-nan Zhang, Lina Yang, Jian-ya Ling, Daniel M. Czajkowsky, Jing-Fang Wang, Xiao-Wei Zhang, Yi-Ming Zhou, Feng Ge, Ming-kun Yang, Qian Xiong, Shu-Juan Guo, Huang-Ying Le, Song-Fang Wu, Wei Yan, Bingya Liu, Heng Zhu, Zhu Chen, Sheng-ce Tao
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Biochemical Research Methods
Huan Qi, Huiqiong Zhou, Daniel Mark Czajkowsky, Shujuan Guo, Yang Li, Nan Wang, Yi Shi, Lifeng Lin, Jingfang Wang, De Wu, Sheng-Ce Tao
MOLECULAR & CELLULAR PROTEOMICS
(2017)
Article
Multidisciplinary Sciences
Zhaowei Xu, Likun Huang, Hainan Zhang, Yang Li, Shujuan Guo, Nan Wang, Shi-hua Wang, Ziqing Chen, Jingfang Wang, Sheng-ce Tao
SCIENTIFIC REPORTS
(2016)
Article
Chemistry, Multidisciplinary
Zonghua Wang, Qiyan Zhao, Menghua Cui, Shichao Pang, Jingfang Wang, Ying Liu, Liming Xie
Article
Biochemical Research Methods
Li Cheng, Cheng-xi Liu, Shuangying Jiang, Sha Hou, Jin-guo Huang, Zi-qing Chen, Yang-yang Sun, Huan Qi, He-wei Jiang, Jing-fang Wang, Yi-ming Zhou, Daniel M. Czajkowsky, Junbiao Dai, Sheng-ce Tao
MOLECULAR & CELLULAR PROTEOMICS
(2018)
Article
Biotechnology & Applied Microbiology
Yunjun Sun, Qiang Zhao, Dasheng Zheng, Xuezhi Ding, Jingfang Wang, Quanfang Hu, Zhiming Yuan, Hyun-Woo Park, Liqiu Xia
BIOTECHNOLOGY LETTERS
(2014)
Review
Biochemistry & Molecular Biology
Xiao-Le Xia, Bo-Tao Fa, Shan Cong, Jing-Fang Wang, Kuo-Chen Chou
CURRENT DRUG METABOLISM
(2014)
Article
Multidisciplinary Sciences
Feifei Xiong, Liliang Xia, Jingfang Wang, Biao Wu, Dengyu Wang, Longfang Yuan, Yating Cheng, Hongying Zhu, Xiaoyan Che, Qinghua Zhang, Guoping Zhao, Ying Wang
Article
Multidisciplinary Sciences
Fei Liu, Yi-Lei Zhao, Xiaolei Wang, Hongbo Hu, Huasong Peng, Wei Wang, Jing-Fang Wang, Xuehong Zhang
Article
Mathematical & Computational Biology
Beili Ying, Shichao Pang, Junchen Yang, Yang Zhong, Jingfang Wang
INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES
(2019)
Letter
Biochemistry & Molecular Biology
Beili Ying, Yang Zhong, Jingfang Wang
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2020)
Article
Biochemical Research Methods
Guiyue Tang, Bingran Xie, Xiangna Hong, Hang Qin, Jingfang Wang, Hai Huang, Pei Hao, Xuan Li
Summary: The study successfully separated the dual activities of A3A and created novel human A3A variants with RNA-specific cytidine deaminase activity through the development of a reporter system and rational mutagenesis design.
ACS SYNTHETIC BIOLOGY
(2021)