Article
Cardiac & Cardiovascular Systems
Jinhong Wei, Wenting Guo, Ruiwu Wang, John Paul Estillore, Darrell Belke, Yong-Xiang Chen, Alexander Vallmitjana, Raul Benitez, Leif Hove-Madsen, S. R. Wayne Chen
Summary: The physiological significance of PKA phosphorylation of RyR2 in the heart is still poorly understood. Recent structural studies have shown that the PKA phosphorylation site S2030 in RyR2 is located within a pathway that is important for the termination of Ca2+ release. We investigated the impact of S2030 mutations on Ca2+ release termination in cells and generated a mouse model to study the role of S2030 in a physiological setting.
CIRCULATION RESEARCH
(2023)
Article
Physiology
Kafa Walweel, Nicole Beard, Dirk F. F. van Helden, Derek R. R. Laver
Summary: Dantrolene is a neutral hydantoin that is used as a skeletal muscle relaxant. It has shown potential as a lead compound for stabilizing overactive cardiac calcium release channels (RyR2) in heart failure. This study found that the inhibitory action of dantrolene on RyR2 depends on the association of RyR2 with FKBP12.6 in addition to CaM, and that RyR2 phosphorylation at S2808 plays a role in this association.
JOURNAL OF GENERAL PHYSIOLOGY
(2023)
Article
Integrative & Complementary Medicine
Longqing Chen, Rongzhen Liu, Weisong Wang, Congcong Tang, Junning Ran, Wei Huang, Shuqi Li, Jianhe Liu
Summary: This study found that CHSSC can reduce the incidence of ventricular arrhythmias following myocardial ischemia by inhibiting the CaMKII/RyR2/FKBP12.6/Ca2+ signaling pathway. CaMKII activation leads to hyperphosphorylation of RyR2, which results in the dissociation of the FKBP12.6-RyR2 complex and increased intracellular Ca2+ content during cardiomyocyte ischemia.
EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
(2022)
Article
Biology
Juan Qin, Jingfeng Zhang, Lianyun Lin, Omid Haji-Ghassemi, Zhi Lin, Kenneth J. Woycechowsky, Filip Van Petegem, Yan Zhang, Zhiguang Yuchi
Summary: This study reveals the disease mechanism of several mutations in PLN by changing its conformation and weakening its interaction with PKA, leading to the reduction of its phosphorylation level. Additionally, another regulatory peptide, called ALN, also regulates SERCA activity through a similar mechanism mediated by PKA.
Article
Multidisciplinary Sciences
Kyle E. Harvey, Emily K. LaVigne, Mohd Saleem Dar, Amy E. Salyer, Evan P. S. Pratt, Paxton A. Sample, Uma Aryal, Humaira Gowher, Gregory H. Hockerman
Summary: The role of RyR2 in pancreatic beta-cell function involves regulation of IRBIT levels and activity, maintenance of insulin content and secretion, and modulation of the proteome possibly through DNA methylation.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Peter J. Harrison, Tereza Vecerkova, Daniel K. Clare, Andrew Quigley
Summary: Membrane proteins play vital roles in biological membranes and are important targets for therapeutics discovery. Cryo-electron microscopy and sample preparation have advanced, but structural study of small MPs (<100 kDa) remains challenging due to low protein abundance, hydrophobicity, and instability. This review discusses successful sample preparation approaches, data processing strategies, and future opportunities for studying sub-100 kDa membrane proteins by cryo-EM.
JOURNAL OF STRUCTURAL BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Laura M. Nederveen-Schippers, Pragya Pathak, Ineke Keizer-Gunnink, Adrie H. Westphal, Peter J. M. van Haastert, Jan Willem Borst, Arjan Kortholt, Victor Skakun
Summary: Protein dimerization plays a crucial role in biological processes, but detecting protein dimers in living cells is challenging. This study presents a methodology, brightness and diffusion global analysis, to measure protein dimerization in living cells. The approach was validated using cell lysates and successfully applied to distinguish different types of protein dimers in living cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Michelle L. Munro, Isabelle van Hout, Hamish M. Aitken-Buck, Ramanen Sugunesegran, Krishna Bhagwat, Philip J. Davis, Regis R. Lamberts, Sean Coffey, Christian Soeller, Peter P. Jones
Summary: The clustering properties of RyR2 were found to be largely unchanged in AF patients, unlike significant differences observed in atrial dilation and cardiomyocyte hypertrophy between patient groups. This suggests that RyR2 cluster remodeling is not a contributing factor to altered channel function and arrhythmogenesis in human AF.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Physiology
Yann Huey Ng, Chidinma A. Okolo, Jeffrey R. Erickson, James C. Baldi, Peter P. Jones
Summary: O-GlcNAcylation is a crucial post-translational modification in the heart, with both harmful and beneficial effects on cardiovascular function. There is a complex interaction between O-GlcNAcylation and phosphorylation in cardiac cells, and this modification also indirectly affects transcription factors and downstream signaling pathways.
Article
Cell Biology
Aojie Wang, Feng Zhou, Congcong Liu, Dongsheng Gao, Ruxi Qi, Yiheng Yin, Sheng Liu, Yuanzhu Gao, Lutang Fu, Yinhe Xia, Yawei Xu, Chuanqing Wang, Zheng Liu
Summary: GETV, a mosquito-borne pathogen, can cause fever and reproductive losses in animals. This study presents the structure of infective GETV and identifies important features that could impact viral immune evasion and host cell invasion. The structural information will aid in the development of antiviral treatments and vaccines.
Review
Biophysics
Elliot T. Sibbles, Helen M. M. Waddell, Valeria Mereacre, Peter P. Jones, Michelle L. Munro
Summary: Cardiac arrhythmias are life-threatening events characterized by an irregular heart rhythm. Mishandling of Ca2+ within heart muscle cells has been shown to be an underlying mechanism of arrhythmogenesis. This review focuses on the role of calsequestrin-2 (CSQ2) in the development of cardiac arrhythmias, specifically how it regulates the activity of the ryanodine receptor (RyR2), a key Ca2+ release channel. The study highlights the importance of understanding CSQ2 and its impact on Ca2+ signaling in order to better comprehend arrhythmic conditions.
BIOPHYSICAL REVIEWS
(2022)
Article
Virology
Xiang-Wei Kong, Xiao Zhang, Guo-Long Bu, Hui-Qin Xu, Yin-Feng Kang, Cong Sun, Qian-Ying Zhu, Run-Bo Ma, Zheng Liu, Yi-Xin Zeng, Mu-Sheng Zeng, Zhu-Long Hu
Summary: Epstein-Barr virus (EBV) is one of the most common human viruses and the first identified human oncogenic virus. It is responsible for a large number of cancer cases and deaths as well as nonmalignant diseases. Currently, there is no prophylactic vaccine available to prevent EBV infection. This study introduces VSV-based EBV vaccines presenting key components of the EBV infection apparatus, gB and gHgL. The vaccines induce strong antibody responses that prevent EBV from infecting epithelial cells and B cells, indicating their potential as prophylactic candidates for preventing EBV-associated diseases.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Yin-Feng Kang, Cong Sun, Jing Sun, Chu Xie, Zhen Zhuang, Hui-Qin Xu, Zheng Liu, Yi-Hao Liu, Sui Peng, Run-Yu Yuan, Jin-Cun Zhao, Mu-Sheng Zeng
Summary: Emerging SARS-CoV-2 variants with multiple mutations raise concerns on vaccine effectiveness. Here, Kang et al. report that a quadrivalent mosaic nanoparticle vaccine displaying spike proteins from the SARS-CoV-2 prototype and three different VOCs confer protection against SARS-CoV-2 variants in mice.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rongrong Shen, Dongchuan Zuo, Kuihao Chen, Yiheng Yin, Kai Tang, Shangwei Hou, Bo Han, Yawei Xu, Zheng Liu, Haijun Chen
Summary: Hypokalemia causes ectopic heartbeats, and this study demonstrates the critical role of K2P1 leak cation channels in ventricular ectopic beats and sudden death in a mouse model. These findings contribute to a better understanding of cardiac issues associated with hypokalemia.
Article
Virology
Cong Sun, Run-Yu Yuan, Chu Xie, Jiu-Feng Sun, Xin-Yan Fang, Yi-Sha Hu, Xiao-Hui Yu, Zheng Liu, Mu-Sheng Zeng, Yin-Feng Kang
Summary: The S1-conjugated nanoparticle vaccine designed in this study has the potential to generate potent and cross-reactive immunity against various SARS-CoV-2 variants, as well as other pathogenic betacoronaviruses.
JOURNAL OF VIROLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jing Liu, Yihen Yin, Jing Ni, Peiyu Zhang, Wei-ming Li, Zheng Liu
Summary: This study reveals a novel molecular mechanism of DUSP7 in cardiovascular disease. High levels of DUSP7 inhibit ERK1/2 phosphorylation and influence the expression of downstream genes, leading to dilated cardiomyopathy and heart failure. These findings provide a new therapeutic target and clinical path for alleviating dilated cardiomyopathy and improving cardiac function.
JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
(2022)
Article
Cell Biology
Yanqun Wang, An Yan, Deyong Song, Chuangchuang Dong, Muding Rao, Yuanzhu Gao, Ruxi Qi, Xiaomin Ma, Qiaoping Wang, Hongguang Xu, Hong Liu, Jing Han, Maoqin Duan, Shuo Liu, Xiaoping Yu, Mengqi Zong, Jianxia Feng, Jie Jiao, Huimin Zhang, Min Li, Beibei Yu, Yanxia Wang, Fanhao Meng, Xiaodan Ni, Ying Li, Zhenduo Shen, Baiping Sun, Xin Shao, Haifeng Zhao, Yanyan Zhao, Rui Li, Yanan Zhang, Guangying Du, Jun Lu, Chunna You, Hua Jiang, Lu Zhang, Lan Wang, Changlin Dou, Zheng Liu, Jincun Zhao
Summary: Researchers isolated two neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. BA7125 showed broad neutralizing activity against all variants, while BA7208 was highly potent neutralizing against all tested SARS-CoV-2 variants except Mu. By combining BA7208 and BA7125, a biparatopic antibody BA7208/7125 that neutralized all tested variants was generated. Cryo-electron microscopy structure analysis showed that the contact residues of these antibodies were conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, BA7208/7125 demonstrated potent therapeutic efficacy against Omicron BA.1 and BA.2 in mice and could be used for effective prophylaxis.
Article
Microbiology
Cong Sun, Yin-Feng Kang, Xin-Yan Fang, Yi-Na Liu, Guo-Long Bu, Ao-Jie Wang, Yan Li, Qian-Ying Zhu, Hua Zhang, Chu Xie, Xiang-Wei Kong, Yong-Jian Peng, Wen-Jie Lin, Ling Zhou, Xin-Chun Chen, Zheng-Zhou Lu, Hui-Qin Xu, Dong-Chun Hong, Xiao Zhang, Ling Zhong, Guo-Kai Feng, Yi-Xin Zeng, Miao Xu, Qian Zhong, Zheng Liu, Mu-Sheng Zeng
Summary: Epstein-Barr virus (EBV) is a global public health concern and there is currently no available prophylactic vaccine against it. This study presents a gB nanoparticle, gB-I53-50 NP, which displays multiple copies of gB and shows improved immunogenicity and protective antibody response in animal models. This vaccine candidate has significant potential in preventing EBV infection.
CELL HOST & MICROBE
(2023)
Article
Cardiac & Cardiovascular Systems
Yunyun Qian, Dongchuan Zuo, Jing Xiong, Yihen Yin, Ruxi Qi, Xiaomin Ma, An Yan, Yawen Yang, Ping Liu, Jingying Zhang, Kai Tang, Wenhui Peng, Yawei Xu, Zheng Liu
Summary: A novel RyR2 mutation A690E associated with sudden cardiac death was identified and its pathogenic basis was investigated in this study. Using animal models and cardiomyocytes, we found that this mutation led to ventricular arrhythmias and abnormal calcium handling, providing a deeper understanding of the mechanism underlying life-threatening cardiac arrhythmia caused by this mutation.
Article
Biochemistry & Molecular Biology
Raquel A. Adams, Zheng Liu, Chongere Hsieh, Michael Marko, W. Jonathan Lederer, M. Saleet Jafri, Carmen Mannella
Summary: The study analyzed a dataset of 68 mitochondrial subvolumes using electron microscopic tomography to investigate the morphological heterogeneity of mitochondria in mammalian cardiomyocytes. The results reveal correlations between mitochondrial size and shape, crista morphology and membrane density, and organelle location within the cells. The findings suggest a rationale for the localization of lamellar mitochondria between myofibrils and provide insights into the remodeling pathway from lamellar to tubular cristae.
CURRENT ISSUES IN MOLECULAR BIOLOGY
(2023)
Letter
Biochemistry & Molecular Biology
Xiaoyu Ma, Yanqun Wang, Yuanzhu Gao, Yiliang Wang, An Yan, Jiantao Chen, Lu Zhang, Peiyi Wang, Jincun Zhao, Zheng Liu
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Cong Sun, Yin-Feng Kang, Yuan-Tao Liu, Xiang-Wei Kong, Hui-Qin Xu, Dan Xiong, Chu Xie, Yi-Hao Liu, Sui Peng, Guo-Kai Feng, Zheng Liu, Mu-Sheng Zeng
Summary: The study demonstrates that the Omicron variant of SARS-CoV-2 has extraordinary potency in immune escape compared to other variants of concern, posing challenges for current antibody therapies and vaccines. Computational interface analysis is shown to be effective in identifying concerning variants early on, providing preliminary guidance for neutralizing antibody therapy.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2022)