Article
Medicine, Research & Experimental
Fang Ye, Thian-Sze Wong, Geng Chen, Zhiyi Zhang, Binghao Zhang, Shiyi Gan, Wei Gao, Jiancheng Li, Zhangsong Wu, Xin Pan, Yang Du
Summary: The study elucidated the activation mechanism of GPR17-Gi complex, revealing the self-activation mechanism of GPR17 and the interaction of Gi with key residues in GPR17.
Article
Multidisciplinary Sciences
Xudong Wang, Chris Neale, Soo-Kyung Kim, William A. Goddard, Libin Ye
Summary: Understanding the roles of intermediate states in GPCR signaling is crucial for studying the activation processes. In this study, conformation-biased mutants were used to enrich the populations of discrete states along the activation pathway of A(2A)R. The results reveal important structural interactions and propose a GPCR activation process modulated by these interactions.
NATURE COMMUNICATIONS
(2023)
Review
Pharmacology & Pharmacy
Ilana B. Kotliar, Emily Lorenzen, Jochen M. Schwenk, Debbie L. Hay, Thomas P. Sakmar
Summary: G protein-coupled receptors (GPCRs) interact with a variety of membrane proteins, but the extent and mechanisms of these interactions are not well understood. RAMPs, a class of GPCR-interacting proteins, have been extensively studied. Recent research suggests that GPCR-RAMP interactions may be more widespread than previously thought. This review summarizes the latest techniques for discovering GPCR-RAMP interactions and their functional consequences, and discusses future research prospects.
PHARMACOLOGICAL REVIEWS
(2023)
Article
Multidisciplinary Sciences
Ruixue Xia, Na Wang, Zhenmei Xu, Yang Lu, Jing Song, Anqi Zhang, Changyou Guo, Yuanzheng He
Summary: The authors used cryo-EM to determine the complex structure of histamine-bound H1R/Gq and proposed a mechanism for ligand-induced receptor activation, providing insights for designing novel antihistamines.
NATURE COMMUNICATIONS
(2021)
Article
Multidisciplinary Sciences
Li-Hua Zhao, Jingyu Lin, Su-Yu Ji, X. Edward Zhou, Chunyou Mao, Dan-Dan Shen, Xinheng He, Peng Xiao, Jinpeng Sun, Karsten Melcher, Yan Zhang, Xiao Yu, H. Eric Xu
Summary: This study presents the structures of CRF2R bound to UCN1 and coupled to G proteins G(11) and G(o), and compares them with the structure of CRF2R bound to G(s), uncovering the structural differences that determine the selective coupling of G protein subtypes by CRF2R.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Genki Terashi, Xiao Wang, Devashish Prasad, Tsukasa Nakamura, Daisuke Kihara
Summary: This study developed a protein structure modeling protocol, DeepMainmast, which combines deep learning and AlphaFold2 to assist main-chain tracing in high-resolution maps, resulting in improved accuracy.
Article
Medicine, Research & Experimental
Thian-Sze Wong, Wei Gao, Geng Chen, Chen Qiu, Guodong He, Fang Ye, Zhangsong Wu, Zicheng Zeng, Yang Du
Summary: GPR21 is a class A orphan GPCR associated with developing T2DM. Cryo-EM and single-particle analysis revealed the high-resolution structure of GPR21-G alpha s complexes, providing direct evidence of their coupling at physiological conditions. Mutagenesis and biochemical analysis showed that ECL2 of GPR21 is essential for transducing intracellular signals via cAMP.
Article
Biochemistry & Molecular Biology
Anthony H. Nguyen, Robert J. Lefkowitz
Summary: G protein-coupled receptors (GPCRs) are a major class of cell-surface receptors involved in cellular signaling, traditionally thought to signal through G proteins or β-arrestin. However, recent studies have shown that some receptors are capable of sustained signaling even after internalization, challenging previous understanding. This new mechanism of sustained signaling presents new research directions and challenges.
Article
Biochemical Research Methods
Xudong Wang, Wenjie Zhao, Sameer Al-Abdul-Wahid, Yiming Lu, Tao Cheng, Jesper J. Madsen, Libin Ye
Summary: The study presents a novel strategy to probe GPCR domain rotation by utilizing specific signal variability, providing insights into receptor activation mechanisms and drug discovery innovation.
BIOCONJUGATE CHEMISTRY
(2021)
Article
Immunology
Ward Vleeshouwers, Koen van den Dries, Sandra de Keijzer, Ben Joosten, Diane S. Lidke, Alessandra Cambi
Summary: This study highlights the modulation of myeloid immune cell function by Prostaglandin E2 (PGE2) through the activation of EP2 and EP4 receptors. EP4 plays a key role in podosome loss in DCs, while both EP2 and EP4 signaling lead to different cAMP production profiles and reciprocal control of signaling pathways. Efficient signaling of both EP2 and EP4 relies on an intact microtubule network, enhancing our understanding of early signaling events in myeloid cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Saehyun Cho, Gijeong Kim, Ji-Joon Song, Carol Cho
Summary: This study presents the cryo-EM structure of AdhE from Vibrio cholerae, revealing similarities and differences with AdhE from Escherichia coli. Divergences in key oligomerization residues in vAdhE lead to unstable spirosomes and lower enzymatic activity, which can be improved by mutating the oligomerization interface to mimic eAdhE. These results support the generality of AdhE spirosome structures and provide insights for targeting vAdhE to attenuate bacterial virulence.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Cell Biology
Gui-Lan Chen, Jian Li, Jin Zhang, Bo Zeng
Summary: Ion channels are the second largest class of drug targets. Cryo-electron microscopy has revolutionized our understanding of ion channel structures and gating mechanisms, but also raised concerns about the pore-forming ability of some previously identified channel proteins. Cross-validation by electrophysiological and structural analyses is proposed as essential for determining molecular identities of novel ion channels.
Review
Biochemistry & Molecular Biology
Libin Ye, Xudong Wang, Aidan McFarland, Jesper J. Madsen
Summary: Advances in X-ray crystallography and cryoelectron microscopy have provided insights into GPCR activation processes, but these static structures have limitations in revealing dynamics and conformational transitions. Developing NMR techniques can lead to a more comprehensive understanding of signaling processes, but challenges remain.
Article
Multidisciplinary Sciences
Bing Rao, Shaobai Li, Deqiang Yao, Qian Wang, Ying Xia, Yi Jia, Yafeng Shen, Yu Cao
Summary: The study demonstrates that human Derlin-1 forms a protein channel for translocation of misfolded proteins, consisting of a large tunnel traversing the ER membrane and a lateral gate within the membrane. This structure differs from the previously reported monomeric yeast Derlin structure, which forms a semi-channel.
Article
Multidisciplinary Sciences
Qiuyan Chen, Manolo Plasencia, Zhuang Li, Somnath Mukherjee, Dhabaleswar Patra, Chun-Liang Chen, Thomas Klose, Xin-Qiu Yao, Anthony A. Kossiakoff, Leifu Chang, Philip C. Andrews, John J. G. Tesmer
Summary: GRKs selectively phosphorylate activated GPCRs for desensitization, with a conserved region at the GRK N terminus playing a crucial role. Cryo-EM reconstructions revealed the binding mechanism between GRK1 and Rho*, providing insights into how a small family of protein kinases can recognize and be activated by numerous GPCRs.
Article
Virology
Sho Miyamoto, Yukiko Muramoto, Keiko Shindo, Yoko Fujita-Fujiharu, Takeshi Morikawa, Ryoma Tamura, Jamie L. Gilmore, Masahiro Nakano, Takeshi Noda
Summary: This study provides evidence that the packaging signals between HA vRNA and PB2 vRNA are important for the selective genome packaging of the influenza A virus. Understanding the packaging mechanism of the influenza virus genome is crucial for developing strategies to combat influenza.
JOURNAL OF VIROLOGY
(2022)
Article
Microbiology
Sho Miyamoto, Masahiro Nakano, Takeshi Morikawa, Ai Hirabayashi, Ryoma Tamura, Yoko Fujita-Fujiharu, Nanami Hirose, Yukiko Muramoto, Takeshi Noda
Summary: This study reveals the importance of the nucleolus in functional RNP formation of influenza A virus. The nucleoprotein temporarily localizes to the nucleolus and a nucleolar localization signal is required for RNP formation. Disruption of the nucleolus inhibits RNP assembly and decreases viral RNA synthesis.
Article
Multidisciplinary Sciences
Jinta Asami, Kanako Terakado Kimura, Yoko Fujita-Fujiharu, Hanako Ishida, Zhikuan Zhang, Yayoi Nomura, Kehong Liu, Tomoko Uemura, Yumi Sato, Masatsugu Ono, Masaki Yamamoto, Takeshi Noda, Hideki Shigematsu, David Drew, So Iwata, Toshiyuki Shimizu, Norimichi Nomura, Umeharu Ohto
Summary: Chronic infection with hepatitis B virus (HBV) requires interaction between the large glycoproteins of the virus envelope (LHBs) and the host entry receptor sodium taurocholate co-transporting polypeptide (NTCP). This study reveals the structures of NTCP and identifies a possible transport route for substrate. Furthermore, the study suggests a binding mode between LHBs and NTCP, which explains naturally occurring HBV-insusceptible mutations in NTCP.
Article
Multidisciplinary Sciences
Yoko Fujita-Fujiharu, Yukihiko Sugita, Yuki Takamatsu, Kazuya Houri, Manabu Igarashi, Yukiko Muramoto, Masahiro Nakano, Yugo Tsunoda, Ichiro Taniguchi, Stephan Becker, Takeshi Noda
Summary: This study determines the structure of the Marburg virus nucleoprotein-RNA complex and provides mechanistic insight into the helical assembly of the nucleocapsid.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hideo Ogiso, Ryoji Suno, Takuya Kobayashi, Masashi Kawami, Mikihisa Takano, Masaru Ogasawara
Summary: Molecular interaction analysis is crucial for studying biomolecular functions and developing new drugs. This study successfully used the SEC-MS method to detect the interaction between low-molecular-weight compounds and membrane proteins without the need for immobilization.
Article
Virology
Yuki Takamatsu, Tomoki Yoshikawa, Takeshi Kurosu, Shuetsu Fukushi, Noriyo Nagata, Masayuki Shimojima, Hideki Ebihara, Masayuki Saijo, Takeshi Noda
Summary: This study identified the localization of VP30 on the surface of ruffled nucleocapsids and revealed its role in nucleocapsid assembly. Phosphorylation of VP30 facilitates its association with nucleocapsid-like structures but does not affect nucleocapsid transport characteristics and virus-like particle budding efficiency.
JOURNAL OF VIROLOGY
(2022)
Article
Cell Biology
Ryoji Suno, Yukihiko Sugita, Kazushi Morimoto, Hiroko Takazaki, Hirokazu Tsujimoto, Mika Hirose, Chiyo Suno-Ikeda, Norimichi Nomura, Tomoya Hino, Asuka Inoue, Kenji Iwasaki, Takayuki Kato, So Iwata, Takuya Kobayashi
Summary: Prostaglandin receptors play important roles in inflammation, immune response, reproduction, and cancer. This study presents the structure of the human EP3-G(i) signaling complex using single-particle cryo-EM and compares it with other subtypes of prostaglandin receptors.
Article
Microscopy
Shangfan Hu, Takeshi Noda
Summary: This article reviews the key characteristics of the Ebola virus and Marburg virus nucleocapsid structures, comparing the similarities and differences between the two viruses. It specifically focuses on the structure of the helical NP-RNA complex, the RNA binding mechanism, and the NP-NP interactions in the helix. Structural analyses reveal a potential mechanism of nucleocapsid assembly and provide potential targets for anti-filovirus drug design.
Article
Biochemistry & Molecular Biology
Hidetsugu Asada, Dohyun Im, Yunhon Hotta, Satoshi Yasuda, Takeshi Murata, Ryoji Suno, So Iwata
Summary: The study uncovers the importance of orexin receptors in regulating the sleep-wake cycle and highlights the potential of developing antagonists for these receptors as novel treatments for sleep-related diseases. The determination of the structure of OX2R bound to lemborexant provides valuable insights into the binding mechanism and furthers our understanding of the pharmacophore models and target selectivity to OXRs.
Article
Multidisciplinary Sciences
Sayaka Deguchi, Kaori Kosugi, Rina Hashimoto, Ayaka Sakamoto, Masaki Yamamoto, Rafal P. Krol, Peter Gee, Ryosuke Negoro, Takeshi Noda, Takuya Yamamoto, Yu-suke Torisawa, Miki Nagao, Kazuo Takayama
Summary: This study investigates the liver pathophysiology in COVID-19 patients and demonstrates that SARS-CoV-2 infection induces hepatic dysfunctions. The combination of anti-viral and immunosuppressive drugs is found to effectively treat hepatic dysfunctions caused by SARS-CoV-2 infection.
Article
Multidisciplinary Sciences
Shangfan Hu, Yoko Fujita-Fujiharu, Yukihiko Sugita, Lisa Wendt, Yukiko Muramoto, Masahiro Nakano, Thomas Hoenen, Takeshi Noda
Summary: In this study, the structure of the Lloviu virus nucleoprotein-RNA helical complex was determined using cryoelectron microscopy. The results showed that the N-terminal region of the nucleoprotein determines the helical arrangement, and identified amino acids involved in helical assembly and viral RNA synthesis. These findings advance our understanding of filovirus nucleocapsid formation and have implications for antiviral therapeutics development.
Article
Microbiology
Sho Miyamoto, Masahiro Nakano, Takeshi Morikawa, Ai Hirabayashi, Ryoma Tamura, Yoko Fujita-Fujiharu, Nanami Hirose, Yukiko Muramoto, Takeshi Noda
Summary: The nucleolus is identified as a crucial site for the formation of functional RNP in the influenza A virus, with NP temporarily localizing to it and relying on a nucleolar localization signal. Disruption of the nucleolus leads to impaired RNP formation and reduced virus replication, highlighting the importance of the nucleolus in the virus life cycle.