Article
Cell Biology
Yamuna Kalyani Mathiharan, Ian W. Glaaser, Yulin Zhao, Michael J. Robertson, Georgios Skiniotis, Paul A. Slesinger
Summary: This study demonstrates how cholesterol affects the structure of GIRK2 channels, revealing that cholesterol modulates the channel by stabilizing the interaction between PIP2 and the channel. This finding may contribute to the development of therapeutics for neurological diseases.
Article
Biochemistry & Molecular Biology
Dongqi Zhang, Yongfeng Liu, Saheem A. Zaidi, Lingyi Xu, Yuting Zhan, Anqi Chen, Jiangtao Guo, Xi-Ping Huang, Bryan L. Roth, Vsevolod Katritch, Vadim Cherezov, Haitao Zhang
Summary: The cryo-EM structure of human AT(1)R complexed with Sar(1)-AngII and G(q) protein reveals the molecular mechanisms of AT(1)R signaling modulation and biased signaling induced by mutations in the major hydrogen bond network. These findings have implications for drug discovery in cardiovascular diseases.
Article
Biology
Amandeep S. Arora, Hsiang-Ling Huang, Ramanpreet Singh, Yoshie Narui, Andrejus Suchenko, Tomoyuki Hatano, Sarah M. Heissler, Mohan K. Balasubramanian, Krishna Chinthalapudi, Pekka Lappalainen
Summary: The structures of actin isoforms have been determined at high resolution, revealing their specific conformations and isoform-specific interfaces. These findings provide important insights into the function of actin isoforms and contribute to our overall understanding of cytoskeletal physiology.
Article
Chemistry, Multidisciplinary
Shuaitong Liang, Zhenjiang Yu, Tianshuai Ma, Haiting Shi, Qingqing Wu, Lijie Ci, Yujin Tong, Jiajun Wang, Zhiwei Xu
Summary: By modulating the electronic structure, it is possible to alleviate internal strain caused by potassium ions and improve the structural stability of battery anodes, providing a new pathway towards highly stable potassium ion batteries.
Article
Multidisciplinary Sciences
Jun Xu, Qinggong Wang, Harald Huebner, Yunfei Hu, Xiaogang Niu, Haoqing Wang, Shoji Maeda, Asuka Inoue, Yuyong Tao, Peter Gmeiner, Yang Du, Changwen Jin, Brian K. Kobilka
Summary: In this study, the authors used cryo-EM and NMR to investigate the mechanisms underlying the signaling versatility of M2R. They found that acetylcholine stabilizes a more heterogeneous M2R-G-protein complex than iperoxo, and LY2119620 modulates agonist efficacy in G-protein and beta-arrestin pathways differently. These findings highlight the importance of conformational dynamics in the complex signaling behavior of GPCRs.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Shangyu Yang, Yong Wang, Feiyang Yu, Rao Cheng, Yiwei Zhang, Dan Zhou, Xuanxiu Ren, Zengqin Deng, Haiyan Zhao
Summary: The rapid spread of monkeypox in multiple countries since May 2022 has caused a global public health threat and international concerns. The monkeypox virus (MPXV) encoded M2 protein plays a role in host immunomodulation by regulating the innate and adaptive immune response. However, the interaction between MPXV M2 and B7 ligands, as well as the structural insight into M2 function, has been unclear.
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Wentong Jiang, Sanduo Zheng
Summary: This study reports the cryoelectron microscopy structures of the GALR1-G(o) and GALR2-G(q) complexes bound to the endogenous ligand galanin or spexin, revealing the structural determinants of GALRs and highlighting the potential role of zinc ion as a modulator of GALR1.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Sreekanth Rajan, Ho Sup Yoon
Summary: Malaria, a prevalent infectious disease, poses a serious challenge due to drug-resistant strains. Adopting a chemo-genomics approach can uncover novel targets and mechanisms of action for better drug targeting. Immunosuppressive drugs have been found to inhibit the growth of the malarial parasite, with peptidyl prolyl cis/trans isomerases (PPIases) as the specific targets. This review summarizes the structural insights on Plasmodium PPIases, their inhibitor complexes, and perspectives on drug discovery.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Azadeh Shahsavar, Peter Stohler, Gleb Bourenkov, Iwan Zimmermann, Martin Siegrist, Wolfgang Guba, Emmanuel Pinard, Steffen Sinning, Markus A. Seeger, Thomas R. Schneider, Roger J. P. Dawson, Poul Nissen
Summary: This study utilized synthetic single-domain antibodies and serial synchrotron crystallography to determine the structure of GlyT1 in complex with an inhibitor, revealing that the inhibitor locks GlyT1 in an inward-open conformation and binds at the intracellular gate of the release pathway. These findings define the mechanism of inhibition and provide insights for the rational design of new, clinically efficacious GlyT1 inhibitors.
Article
Chemistry, Medicinal
Yuguang Zhao, Fredrik Svensson, David Steadman, Sarah Frew, Amy Monaghan, Magda Bictash, Tiago Moreira, Rod Chalk, Weixian Lu, Paul Fish, E. Yvonne Jones
Summary: Notum inhibitors can restore Wnt signaling which may be therapeutic for diseases such as osteoporosis and Alzheimer's. A novel class of covalent Notum inhibitors, 4-(indolin-1-yl)-4oxobutanoate esters, and their covalent adduct formation mechanisms were identified. Insights into the inhibition of Notum catalysis could lead to the development of more potent inhibitors.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Endocrinology & Metabolism
Brice Beinsteiner, Isabelle M. L. Billas, Dino Moras
Summary: Hepatocyte Nuclear Factor 4 (HNF4) is a transcription factor that plays a crucial role in regulating liver-specific gene expression. Dysregulation of HNF4 is associated with human diseases like type I diabetes and hemophilia. This review focuses on the structures of HNF4 and its impact on the receptor's structure-function relationship.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Wolfram Seifert-Davila, Mathias Girbig, Luis Hauptmann, Thomas Hoffmann, Sebastian Eustermann, Christoph W. Mueller
Summary: Transcription factor (TF) IIIC recruits RNA polymerase (Pol) III to target genes by recognizing intragenic A- and B-box motifs. Cryo-electron microscopy structures revealed that the tau B module of TFIIIC recognizes the B-box through DNA shape and sequence readout. TFIIIC220 acts as a linker connecting the tau A and tau B subcomplexes, facilitating scanning for A-boxes and Pol III activation by TFIIIB.
Review
Pharmacology & Pharmacy
Ming-Yue Wu, Er-Jin Wang, Du Feng, Min Li, Richard D. Ye, Jia-Hong Lu
Summary: Autophagy is closely related to autoimmune diseases, with potential therapeutic effects of autophagy modulators in treating these diseases, which require further research and exploration.
ACTA PHARMACEUTICA SINICA B
(2021)
Article
Multidisciplinary Sciences
Yuyuan Zheng, Lei Ding, Xianhui Meng, Meg Potter, Alison L. Kearney, Jie Zhang, Jie Sun, David E. James, Guang Yang, Chun Zhou
Summary: Research has revealed that SIN1 is a vital component of mTORC2 and can interact with Ras family small GTPases through its Ras-binding domain (RBD). The association between Ras and SIN1/mTORC2 can potentially impact both mTORC2 and Ras-ERK pathways. By determining the high-resolution structures of HRas/KRas-SIN1 RBD complexes, researchers have identified the detailed interaction interface. Mutations in critical interface residues disrupt the Ras-SIN1 interaction, and in SIN1 knockout cells, it has been shown that the Ras-SIN1 association promotes SGK1 activity but inhibits insulin-induced ERK activation. Comparison with other Ras-binding proteins and experimental assays suggest that the association between HRas and SIN1 RBD is weaker than HRas-Raf1 RBD but slightly stronger than HRas-PI3K RBD, potentially explaining the different outcomes of insulin or EGF stimulation. Additionally, a Ras dimerization interface critical for Ras oligomerization has been uncovered. These findings contribute to our understanding of the Ras-SIN1 association and the cross-talk between growth factor-stimulated pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yan Zhang, Xiaoyun Pang, Jian Li, Jiashu Xu, Victor W. Hsu, Fei Sun
Summary: By using cryoelectron microscopy, researchers have revealed the protein lattice formed by SNX1, which helps to understand how it functions in generating transport carriers. Comparing the structure of SNX1 with that of an endosomal coat complex formed by retromer coupled to a SNX provides insights into the molecular organization of SNX and the intermediary stages of assembly leading to the formation of the complex on the membrane.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Multidisciplinary Sciences
Jizong Wang, Meijuan Hu, Jia Wang, Jinfeng Qi, Zhifu Han, Guoxun Wang, Yijun Qi, Hong-Wei Wang, Jian-Min Zhou, Jijie Chai
Article
Multidisciplinary Sciences
Jizong Wang, Jia Wang, Meijuan Hu, Shan Wu, Jinfeng Qi, Guoxun Wang, Zhifu Han, Yijun Qi, Ning Gao, Hong-Wei Wang, Jian-Min Zhou, Jijie Chai
Article
Plant Sciences
Jizong Wang, Jijie Chai
Editorial Material
Cell Biology
Jijie Chai
Review
Plant Sciences
Yehui Xiong, Zhifu Han, Jijie Chai
CURRENT OPINION IN PLANT BIOLOGY
(2020)
Article
Chemistry, Medicinal
Li Sun, Youmei Peng, Wenquan Yu, Yan Zhang, Lan Liang, Chuanjun Song, Jiao Hou, Yan Qiao, Qingduan Wang, Jingyu Chen, Mengli Wu, Dongwei Zhang, Ertong Li, Zhifu Han, Qingxia Zhao, Xia Jin, Bailing Zhang, Zhiwei Huang, Jijie Chai, Jian-Hua Wang, Junbiao Chang
JOURNAL OF MEDICINAL CHEMISTRY
(2020)
Review
Biology
Jizong Wang, Jijie Chai
SCIENCE CHINA-LIFE SCIENCES
(2020)
Article
Microbiology
Lisa K. Mahdi, Menghang Huang, Xiaoxiao Zhang, Ryohei Thomas Nakano, Leila Brule Kopp, Isabel M. L. Saur, Florence Jacob, Viera Kovacova, Dmitry Lapin, Jane E. Parker, James M. Murphy, Kay Hofmann, Paul Schulze-Lefert, Jijie Chai, Takaki Maekawa
CELL HOST & MICROBE
(2020)
Review
Plant Sciences
Wen Song, Alexander Forderer, Dongli Yu, Jijie Chai
Summary: Plants use both membrane-bound and intracellular immune receptors to distinguish self from invaders, initiating pattern-triggered immunity and effector-triggered immunity respectively. Pathogens can overcome pattern-triggered immunity by secreting effectors, which are specifically recognized by intracellular NLRs receptors.
Article
Multidisciplinary Sciences
Shoucai Ma, Dmitry Lapin, Li Liu, Yue Sun, Wen Song, Xiaoxiao Zhang, Elke Logemann, Dongli Yu, Jia Wang, Jan Jirschitzka, Zhifu Han, Paul Schulze-Lefert, Jane E. Parker, Jijie Chai
Article
Developmental Biology
Liang Zhang, Daniel DeGennaro, Guangzhong Lin, Jijie Chai, Elena D. Shpak
Summary: The shoot apical meristem is a crucial reservoir of stem cells in plants, with its size regulated by a balance of stem cell replenishment and cell incorporation into organ primordia. The WUS/CLV negative feedback loop plays a central role in SAM size regulation, depending on accurate spatial expression of WUS and CLV3. A signaling pathway involving ERf receptors and EPFL ligands restricts SAM width and promotes leaf initiation by inhibiting the expression of WUS and CLV3 in the periphery and confining them to the center of the SAM.
Article
Microbiology
Saskia Bauer, Dongli Yu, Aaron W. Lawson, Isabel M. L. Saur, Lamprinos Frantzeskakis, Barbara Kracher, Elke Logemann, Jijie Chai, Takaki Maekawa, Paul Schulze-Lefert
Summary: Barley powdery mildew caused by the fungus Blumeria graminis forma specialis hordei (Bgh) can lead to annual yield losses of 15% in this cereal crop. Host plants have evolved a variety of disease resistance genes in response to diverse effector molecules secreted by Bgh to modify the immune status and physiology of the host. Among these genes, the Mla resistance gene has undergone diversification in the host population and plays a key role in providing isolate-specific immunity against Bgh.
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
Chen Liu, Lianping Shen, Yu Xiao, David Vyshedsky, Chao Peng, Xiang Sun, Zhiwen Liu, Lijun Cheng, Hua Zhang, Zhifu Han, Jijie Chai, Hen-Ming Wu, Alice Y. Cheung, Chao Li
Summary: This study elucidates the precise communication mechanism between pollen and pistil in angiosperms. Pollen competes with stigma peptides through binding, leading to a decrease in stigmatic ROS levels after pollination, facilitating pollen hydration and germination.
Correction
Plant Sciences
Pingping Qian, Wen Song, Toshiya Yokoo, Ayako Minobe, Guodong Wang, Takashi Ishida, Shinichiro Sawa, Jijie Chai, Tatsuo Kakimoto