Article
Multidisciplinary Sciences
Viola Nahse, Camilla Raiborg, Kia Wee Tan, Sissel Mork, Maria Lyngaas Torgersen, Eva Maria Wenzel, Mireia Nager, Veijo T. T. Salo, Terje Johansen, Elina Ikonen, Kay Oliver Schink, Harald Stenmark
Summary: DFCP1 is an ATPase located on omegasomes and plays a crucial role in selective autophagy by promoting the constriction of large omegasomes. It is essential for maintaining cellular homeostasis by removing damaged organelles and protein aggregates.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Kiran S. Toti, John R. Jimah, Veronica Salmaso, Jenny E. Hinshaw, Kenneth A. Jacobson
Summary: This study investigates the impact of the North and South conformations of guanine nucleotides on dynamin-mediated membrane constriction and reveals that the activity of dynamin is dependent on the conformational state of the GTP nucleotide. However, natural dynamin structures predominantly exhibit the (S)-conformation, presenting a mismatch with the required (N) vs. (S) for GTP analogues in the dynamin-mediated process.
Article
Biochemistry & Molecular Biology
Sarah El Kharraz, Vanessa Dubois, Martin E. van Royen, Adriaan B. Houtsmuller, Ekatarina Pavlova, Nina Atanassova, Tien Nguyen, Arnout Voet, Roy Eerlings, Florian Handle, Stefan Prekovic, Elien Smeets, Lisa Moris, Wout Devlies, Claes Ohlsson, Matti Poutanen, Kevin J. Verstrepen, Geert Carmeliet, Kaisa-Mari Launonen, Laura Helminen, Jorma J. Palvimo, Claude Libert, Dirk Vanderschueren, Christine Helsen, Frank Claessens
Summary: Dimerization of the ligand-binding domain of the androgen receptor (AR) is crucial for transcriptional regulation and proper functioning of AR. Mutations disrupting LBD dimerization can lead to significant effects, as demonstrated in a mouse model in this study.
Article
Immunology
Leying Zhang, Yuanjing Li, Zhenyang Zhao, Jiabao Cai, Shuxin Zhao, Ling Yang
Summary: This study found that the expression of NLR family in the maternal thymus is changed during pregnancy stages, which may be related to the modulation of maternal thymic immune responses and beneficial for normal pregnancy in sheep.
Article
Multidisciplinary Sciences
David Paul, Omer Stern, Yvonne Vallis, Jatinder Dhillon, Andrew Buchanan, Harvey McMahon
Summary: The study reveals an aggregation-dependent endocytosis pathway that facilitates uptake and degradation of protein aggregates. This mechanism of managing exogenous proteotoxicity is crucial for cellular homeostasis. The findings highlight the importance of the response to denaturation of extracellular proteins.
NATURE COMMUNICATIONS
(2023)
Review
Biochemistry & Molecular Biology
Simran Chhabra, Manjula Kalia
Summary: Guanylate-binding proteins (GBPs) are immune GTPases induced by interferon and are involved in various physiological processes. They play important roles in bacterial and viral infections, but their functions in viral infections are still not well understood. GBPs have diverse antiviral roles including inhibition of viral replication, blocking of viral protein processing, and targeting viral proteins for degradation. However, viral proteins can also counteract the antiviral effects of GBPs. This review discusses the emerging functional roles of GBPs in viral infections.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2023)
Article
Chemistry, Multidisciplinary
Hui Wu, Linyan Zheng, Neng Ling, Liyan Zheng, Yulin Du, Qiang Zhang, Yue Liu, Weihong Tan, Liping Qiu
Summary: Chemically synthetic receptors, such as Ts-pHLIP-Pr, have been developed to equip cells with artificial signaling pathways and enable interaction with the outer world. Through conformational switch of pHLIP, specific proteins can be recruited to trigger downstream signaling cascades upon sensing external pH stimuli. This receptor can be extended to induce T-cell activation via low-pH environment-induced directional movement of cytoplasmic ZAP70.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biology
Sho W. Suzuki, Akihiko Oishi, Nadia Nikulin, Jeff R. Jorgensen, Matthew G. Baile, Scott D. Emr
Summary: The study uncovered a novel endosomal retrieval pathway mediated by Mvp1 protein, which deforms and cuts the endosomal membrane to release recycling tubules, distinct from traditional pathways. Additionally, human homolog SNX8, also implicated in Alzheimer's disease, participates in the formation of endosomal recycling tubules, revealing a conserved mechanism from yeast to humans.
Article
Biochemistry & Molecular Biology
Ryan S. Ramos, Rosivaldo S. Borges, Joao S. N. de Souza, Inana F. Araujo, Mariana H. Chaves, Cleydson B. R. Santos
Summary: This study aimed to identify potential inhibitors for SARS-CoV-2 ACE2 receptors and investigate their mechanism of action using molecular modeling and theoretical determination of biological activity. Through virtual screening and docking studies, several molecules with antiviral potential were identified. The pharmacokinetic and toxicological studies showed these molecules to have low toxicity and good bioavailability.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Environmental Sciences
Da-Woon Jung, Da-Hyun Jeong, Hee-Seok Lee
Summary: This study investigated the endocrine disrupting mechanisms of eight selected pesticide products on the human androgen receptor (hAR). The results showed that all eight pesticides acted as antagonists to the AR at non-toxic concentrations, confirmed through specificity control tests. Additionally, none of the pesticides induced AR homo-dimerization in the Bioluminescence Resonance Energy Transfer-based assay.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Article
Biology
Keijun Kakihara, Kengo Asamizu, Kei Moritsugu, Masahide Kubo, Tetsuya Kitaguchi, Akinori Endo, Akinori Kidera, Mitsunori Ikeguchi, Akira Kato, Masayuki Komada, Toshiaki Fukushima
Summary: This study identified amino acids 645-684 of USP8 as an autoinhibitory region and suggested that the release of USP8 autoinhibition may underlie Cushing's disease. The findings also indicate that 14-3-3 inhibits USP8 activity partly by enhancing the interaction between the WW-like and USP domains.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Shwetha Srinivasan, Raju Regmi, Xingcheng Lin, Courtney A. Dreyer, Xuyan Chen, Steven D. Quinn, Wei He, Matthew A. Coleman, Kermit L. Carraway, Bin Zhang, Gabriela S. Schlau-Cohen
Summary: In this study, the authors show that transmembrane conformational coupling is the first step in EGFR signaling, providing evidence for the existence of transmembrane intramolecular conformational changes in a single pass membrane protein. They also found that ligand binding induces intracellular conformational changes within monomeric EGFR, and implicate a series of electrostatic interactions in the conformational coupling. These results suggest that intramolecular transmembrane conformational changes upon ligand binding may be common to single-pass membrane proteins.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Biochemistry & Molecular Biology
Jeremy S. Morris, Joseph M. Jez
Summary: In this study, the X-ray crystal structures of APS kinase domains from human PAPS synthase were determined, showing the dynamic substrate recognition and a regulatory redox switch similar to plant APS kinases.
Article
Biochemistry & Molecular Biology
Zhen-Lu Li, Carla Mattos, Matthias Buck
Summary: The article explores the importance of dynamic allostery in protein-protein interactions, revealing the impact of protein fluctuations on protein association processes, and investigates the influence of point mutations and ambient temperature on protein dynamics and interactions.
Review
Immunology
John Le, Yathushigan Kulatheepan, Samithamby Jeyaseelan
Summary: The respiratory system has various innate immune mechanisms to cope with microbial infections and limit tissue damage. Macrophages, neutrophils, dendritic cells, epithelial cells, and endothelial cells play key roles in this immune response. Recognition of invading microorganisms by the myeloid and structural cells of the respiratory system triggers a signaling cascade that leads to the activation of transcription factors, induction of cytokines/chemokines, recruitment of immune cells, and subsequent clearance of microbes.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Chemistry, Medicinal
Shujing Xu, Lin Sun, Alexej Dick, Waleed A. Zalloum, Tianguang Huang, Megan E. Meuser, Xujie Zhang, Yucen Tao, Srinivasulu Cherukupalli, Dang Ding, Xiao Ding, Shenghua Gao, Xiangyi Jiang, Dongwei Kang, Erik De Clercq, Christophe Pannecouque, Simon Cocklin, Xinyong Liu, Peng Zhan
Summary: By modifying the structure of PF74, two potent compounds with significantly improved metabolic stability were identified, showing promising antiviral activity against both HIV-1 and HIV-2. These compounds represent a blueprint for developing a new generation of HIV treatment regimens with novel structures and enhanced metabolic stability.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Alexej Dick, Megan E. Meuser, Simon Cocklin
Summary: This study isolated and characterized CA proteins from different HIV-1 subtypes and compared their assembly and inhibitor binding properties. It was found that HIV-1 CA from Glade Al showed altered interactions with NUP-153, which may affect the nuclear import of CA core structures. The in silico generated models of non-B HIV-1 CA protein were also shown to be useful for understanding and predicting the biology and mechanism of action of antiviral drugs.
Article
Biology
Yinbo Huo, Weiping Sun, Tiezhu Shi, Song Gao, Min Zhuang
Summary: This study reveals that mitofusins (MFNs) regulate the contact between mitochondria and peroxisomes, thereby playing important roles in inter-organelle metabolism regulation and signaling.
COMMUNICATIONS BIOLOGY
(2022)
Article
Medicine, Research & Experimental
Changzhi Li, Hongjuan Zhou, Lingling Guo, Dehuan Xie, Huiping He, Hong Zhang, Yixiu Liu, Lixia Peng, Lisheng Zheng, Wenhua Lu, Yan Mei, Zhijie Liu, Jie Huang, Mingdian Wang, Ditian Shu, Liuyan Ding, Yanhong Lang, Feifei Luo, Jing Wang, Bijun Huang, Peng Huang, Song Gao, Jindong Chen, Chao-Nan Qian
Summary: This study established an anti-coronavirus drug screening platform and identified three potential compounds with anti-coronavirus activity. TS-984 showed strong inhibitory effects and has the potential to be developed into an effective anti-coronavirus drug.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Xiangkai Ji, Jing Li, Prem Prakash Sharma, Xiangyi Jiang, Brijesh Rathi, Zhen Gao, Lide Hu, Dongwei Kang, Erik De Clercq, Simon Cocklin, Chuanfeng Liu, Christophe Pannecouque, Alexej Dick, Xinyong Liu, Peng Zhan
Summary: This study investigated the inhibitory activity of phenylalanine derivatives against HIV. The results showed that compound I-19 exhibited the best anti-HIV-1 activity, while compound I-14 displayed excellent HIV-2 inhibitory activity. Additionally, the binding ability of these compounds to HIV was confirmed. These findings contribute to the discovery of effective anti-HIV drugs.
Article
Multidisciplinary Sciences
Tobias Bock-Bierbaum, Kathrin Funck, Florian Wollweber, Elisa Lisicki, Karina von der Malsburg, Alexander von der Malsburg, Janina Laborenz, Jeffrey K. Noel, Manuel Hessenberger, Sibylle Jungbluth, Carola Bernert, Severine Kunz, Dietmar Riedel, Hauke Lilie, Stefan Jakobs, Martin van der Laan, Oliver Daumke
Summary: Mitochondrial cristae membranes are where oxidative phosphorylation occurs in cells, and cristae junctions serve as selective entry gates into the cristae space. The Mic60-Mic19 subcomplex acts as a molecular strut, controlling the architecture and function of cristae junctions.
Article
Biochemistry & Molecular Biology
Xujie Zhang, Lin Sun, Shujing Xu, Xiaoyu Shao, Ziyi Li, Dang Ding, Xiangyi Jiang, Shujie Zhao, Simon Cocklin, Erik De Clercq, Christophe Pannecouque, Alexej Dick, Xinyong Liu, Peng Zhan
Summary: The AIDS pandemic remains significant, and the HIV capsid protein has become an interesting therapeutic target. This study introduces a novel series of 2-pyridone-bearing phenylalanine derivatives as HIV capsid modulators, with compounds FTC-2 and TD-1a showing potential anti-HIV activity.
Article
Biochemistry & Molecular Biology
Shujing Xu, Lin Sun, Waleed A. Zalloum, Tianguang Huang, Xujie Zhang, Dang Ding, Xiaoyu Shao, Xiangyi Jiang, Fabao Zhao, Simon Cocklin, Erik De Clercq, Christophe Pannecouque, Alexej Dick, Xinyong Liu, Peng Zhan
Summary: In this study, a series of piperazinone phenylalanine derivatives with a terminal indole or benzene ring were designed and synthesized. The antiviral activity and mechanism of action were assessed. F-2-7f exhibited moderate antiviral activity against HIV-1 and showed a preference for inhibiting HIV-2. Molecular dynamics simulation revealed that F-2-7f bound to the HIV-1 CA protein. Computational analysis predicted improved drug-like properties and metabolic stability for F-2-7f.
Article
Biochemistry & Molecular Biology
Yingjie Guo, Huan Zhang, Chen Yan, Birong Shen, Yue Zhang, Xiangyang Guo, Sha Sun, Fan Yu, Jiayun Yan, Ronghe Liu, Qianping Zhang, Di Zhang, Haiyang Liu, Yang Liu, Yaoyao Zhang, Wenlei Li, Jiangyu Qin, He Lv, Zhaoxia Wang, Yun Yuan, Jie-Feng Yang, Ya-Ting Zhong, Song Gao, Bing Zhou, Lei Liu, Deling Kong, Xiaojiang Hao, Junjie Hu, Quan Chen
Summary: Membrane dynamics play a crucial role in maintaining the integrity and function of mitochondria, and defective mitochondrial fusion is implicated in various diseases. This study introduces a small molecule agonist, S89, that specifically enhances mitochondrial fusion by targeting endogenous MFN1. S89 interacts with a specific region of MFN1, promoting GTP hydrolysis and vesicle fusion. By boosting endogenous MFN1, S89 restores mitochondrial and cellular defects caused by mitochondrial DNA mutations and other stressors. Notably, S89 also protects against mitochondrial damage induced by ischemia/reperfusion injury in the mouse heart. These findings contribute to our understanding of the priming mechanism for MFNs and offer a potential therapeutic strategy for mitochondrial diseases.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Yao Wang, Tao Qi, Jingtong Liu, Yuan Yang, Ziwen Wang, Ying Wang, Tianyi Wang, Miaomiao Li, Mingqing Li, Daru Lu, Alex Chia Yu Chang, Li Yang, Song Gao, Yongming Wang, Feng Lan
Summary: The CRISPR-Cas system can treat autosomal dominant diseases by disrupting mutant alleles through nonhomologous end joining (NHEJ). However, current CRISPR-Cas systems cannot differentiate many single-nucleotide mutations from wild-type alleles. We identified Cas12j-8 as an ideal genome editor with comparable activity to AsCas12a and Un1Cas12f1. Cas12j-8 is a highly specific nuclease sensitive to single-nucleotide mismatches in the protospacer adjacent motif (PAM)-proximal region. It enables allele-specific disruption of genes with single-nucleotide polymorphisms (SNPs) and has potential therapeutic applications.
Article
Biochemistry & Molecular Biology
Qing Zhou, Yuhao Yang, Zhanxue Xu, Kai Deng, Zhenzhen Zhang, Jiawei Hao, Ni Li, Yanling Wang, Ziwen Wang, Haihang Chen, Yang Yang, Fei Xiao, Xiaohong Zhang, Song Gao, Yi-Ping Li
Summary: ATAD1 plays a crucial role in maintaining mitochondrial homeostasis and combating viral infection. HCV infection induces mitochondrial fragmentation and enhances the pro-infection effect of ATAD1 knockout. ATAD1 interacts with HCV NS5B protein and promotes its degradation, thereby exerting its antiviral function.
Article
Multidisciplinary Sciences
Alexander von der Malsburg, Gracie M. Sapp, Kelly E. Zuccaro, Alexander von Appen, Frank R. Moss, Raghav Kalia, Jeremy A. Bennett, Luciano A. Abriata, Matteo Dal Peraro, Martin van der Laan, Adam Frost, Halil Aydin
Summary: This study reveals the molecular mechanisms of OPA1-dependent membrane remodeling and fusion, providing a structural framework for understanding how human OPA1 shapes mitochondrial morphology and showing how human disease mutations compromise OPA1 functions.
Article
Immunology
Jie-Feng Yang, Xudong Xing, Li Luo, Xin-Wei Zhou, Jian-Xiong Feng, Kang-Bo Huang, Huashan Liu, Shanzhao Jin, Yi-Na Liu, Shi-Hui Zhang, Yi-Hui Pan, Bing Yu, Jin-Yu Yang, Yu-Lu Cao, Yun Cao, Cliff Y. Yang, Yuan Wang, Yuxia Zhang, Jiang Li, Xiaojun Xia, Tiebang Kang, Rui-Hua Xu, Ping Lan, Jun-Hang Luo, Hui Han, Fan Bai, Song Gao
Summary: This study reveals the positive correlation between MFN2 expression and the prognosis of multiple cancers. MFN2 enhances mitochondria-ER contact in tumor-infiltrating CD8(+) T cells by interacting with ER-embedded SERCA2, facilitating the mitochondrial Ca2+ influx required for efficient mitochondrial metabolism. Elevating MFN2 expression in CD8(+) T cells improves the efficacy of cancer immunotherapy by increasing mitochondria-ER contact.
SCIENCE IMMUNOLOGY
(2023)
Article
Oncology
Li Luo, Denghui Wei, Yihui Pan, Qiu-Xia Wang, Jian-Xiong Feng, Bing Yu, Tiebang Kang, Junhang Luo, Jiefeng Yang, Song Gao
Summary: In this study, it was found that the mitochondrial protein mitofusin-2 (MFN2) suppresses tumor development and metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the epidermal growth factor receptor (EGFR) signaling pathway. MFN2 expression is down-regulated in ccRCC and is associated with favorable prognosis. The study also showed that MFN2 interacts with Rab21 to dock endocytosed EGFR to mitochondria, where it is subsequently inactivated by the tyrosine-protein phosphatase receptor type J (PTPRJ), leading to inhibition of tumor growth and metastasis.
CANCER COMMUNICATIONS
(2023)
Article
Cell Biology
Ying Gao, Xueping Zheng, Boyang Chang, Yujie Lin, Xiaodan Huang, Wen Wang, Shirong Ding, Weixiang Zhan, Shang Wang, Beibei Xiao, Lanqing Huo, Youhui Yu, Yilin Chen, Run Gong, Yuanzhong Wu, Ruhua Zhang, Li Zhong, Xin Wang, Qiuyan Chen, Song Gao, Zhengfan Jiang, Denghui Wei, Tiebang Kang
Summary: Activated STING can be transferred between cells to promote antitumor immunity, a process triggered by non-canonical autophagy mediated by RAB22A. RAB22A induces the fusion of non-canonical autophagosomes with early endosomes, forming a new organelle called Rafeesome, and suppresses fusion with lysosomes. The inner vesicle of non-canonical autophagosome, containing activated STING, is secreted as R-EV, which induces the release of IFN beta from recipient cells and promotes antitumor immunity.