Article
Virology
Luis Adrian De Jesus-Gonzalez, Selvin Noe Palacios-Rapalo, Jose Manuel Reyes-Ruiz, Juan Fidel Osuna-Ramos, Carlos Noe Farfan-Morales, Carlos Daniel Cordero-Rivera, Bulmaro Cisneros, Ana Lorena Gutierrez-Escolano, Rosa Maria del Angel
Summary: Recent evidence suggests that nuclear elements play a role in the replication of Flaviviruses, with certain viral proteins being imported into the nucleus. Furthermore, nuclear localization of these proteins has been observed in infected cells. The presence of ZIKV NS3 in the nucleus has been investigated, showing that NS3 is imported into the nucleus via the importin pathway and exported back to the cytoplasm.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Yiwei Chen, Kai Xu, Luca Piccoli, Mathilde Foglierini, Joshua Tan, Wenjie Jin, Jason Gorman, Yaroslav Tsybovsky, Baoshan Zhang, Boubacar Traore, Chiara Silacci-Fregni, Claudia Daubenberger, Peter D. Crompton, Roger Geiger, Federica Sallusto, Peter D. Kwong, Antonio Lanzavecchia
Summary: This study demonstrates that Plasmodium falciparum RIFINs can bind to LILRB1 through D3, and inserting receptor domains into the VH-CH1 elbow can generate novel antibodies, as shown by a naturally selected example.
Article
Cell Biology
Swapnil Rohidas Shinde, David U. Mick, Erika Aoki, Rachel B. Rodrigues, Steven P. Gygi, Maxence V. Nachury
Summary: Many G protein-coupled receptors (GPCRs) within cilia require TOM1L2 and the BBSome for their regulated exit from cilia. TOM1L2 directly binds to UbK63 chains and the BBSome, enabling the retrieval of UbK63-tagged proteins by the ciliary trafficking machinery. This study provides insight into the molecular basis of UbK63 recognition and the role of TOM1L2 in ciliary protein clearance.
DEVELOPMENTAL CELL
(2023)
Article
Microbiology
Hangil Kim, Hanako Shimura, Kae Sueda, Chikara Masuta
Summary: RNA silencing is an important defense mechanism of host plants against viral infection. Cucumber mosaic virus encodes a protein called 2b, which suppresses RNA silencing. This study found that the phosphorylation of 2b at position 28 negatively regulates its RNA silencing suppression activity by affecting its nuclear localization. The study also discovered that 2b's transport between the nucleus and cytoplasm is similar to that of Argonaute proteins, suggesting that 2b manipulates its nucleocytoplasmic trafficking to track down its targets in the RNA silencing pathway. The efficient RNA silencing suppression activity of 2b is maintained by a balance of phosphorylation and dephosphorylation and is coupled to importin/exportin-mediated shuttling between the nucleus and cytoplasm.
Article
Multidisciplinary Sciences
Khuram U. Ashraf, Rie Nygaard, Owen N. Vickery, Satchal K. Erramilli, Carmen M. Herrera, Thomas H. McConville, Vasileios I. Petrou, Sabrina I. Giacometti, Meagan Belcher Dufrisne, Kamil Nosol, Allen P. Zinkle, Chris L. B. Graham, Michael Loukeris, Brian Kloss, Karolina Skorupinska-Tudek, Ewa Swiezewska, David I. Roper, Oliver B. Clarke, Anne-Catrin Uhlemann, Anthony A. Kossiakoff, M. Stephen Trent, Phillip J. Stansfeld, Filippo Mancia
Summary: This study presents the structures of WaaL from Cupriavidus metallidurans and provides molecular details and a mechanistic model for lipopolysaccharide maturation.
Article
Multidisciplinary Sciences
Chongzhao You, Yumu Zhang, Youwei Xu, Peiyu Xu, Zhen Li, Huadong Li, Sijie Huang, Zecai Chen, Jingru Li, Eric Xu, Yi Jiang
Summary: Motilin is an endogenous peptide hormone that is mainly expressed in the human gastrointestinal tract. It activates the motilin receptor (MTLR), a type of G protein-coupled receptor (GPCR), and promotes GI motility. This study presents the structures of MTLR bound to motilin and erythromycin, revealing the recognition mechanism of these ligands. The findings provide insights into the physiological regulation of MTLR and offer guidance for drug design targeting MTLR for the treatment of GI motility disorders.
Article
Multidisciplinary Sciences
Sarah A. Mosure, Timothy S. Strutzenberg, Jinsai Shang, Paola Munoz-Tello, Laura A. Solt, Patrick R. Griffin, Douglas J. Kojetin
Summary: Heme is an endogenous ligand for REV-ERB nuclear receptors, regulating their activity by binding with corepressor NCoR and influencing the thermodynamic interaction profile between NCoR and REV-ERBβ. This finding sheds light on the mechanism of heme-dependent REV-ERB activity.
Article
Multidisciplinary Sciences
Xiaopan Gao, Huabin Tian, Kaixiang Zhu, Qing Li, Wei Hao, Linyue Wang, Bo Qin, Hongyu Deng, Sheng Cui
Summary: This study reveals the molecular basis for the antagonistic function of Sarbecovirus ORF6 and suggests a potential strategy for immunosuppressive drug development using ORF6 CTT-derived peptides.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Medicinal
Rachel A. Rowlands, Qiuyan Chen, Renee A. Bouley, Larisa Avramova, John J. G. Tesmer, Andrew D. White
Summary: The ability of GRK2 and GRK5 to regulate GPCR desensitization makes them attractive targets for heart failure and cancer treatment. Previous research showed potential for selective inhibition of GRK5 over GRK2 using a specific residue, but the inhibitors were not very potent. A new study successfully adapted an indolinone scaffold with covalent warheads, creating compounds with high selectivity for GRK5 and low nanomolar potency.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Amartya Mishra, Jan Naseer Kaur, Daniel I. McSkimming, Eva Hegedusova, Ashutosh P. Dubey, Martin Ciganda, Zdenek Paris, Laurie K. Read
Summary: The T. brucei RBP DRBD18 associates with Mex67/Mtr2 and plays a role in regulating the accumulation of certain mRNAs in the nucleus, affecting their nuclear export. This study reveals the mechanism by which DRBD18 promotes the selective nuclear export of mRNAs in T. brucei.
MOLECULAR MICROBIOLOGY
(2021)
Article
Oncology
Sanmei Wang, Leopold Sellner, Lei Wang, Tim Sauer, Brigitte Neuber, Wenjie Gong, Sophia Stock, Ming Ni, Hao Yao, Christian Kleist, Anita Schmitt, Carsten Mueller-Tidow, Michael Schmitt, Maria-Luisa Schubert
Summary: CAR T cells targeting CD19 have shown impressive clinical responses in lymphoid malignancies, but resistance and relapse remain challenges. Combining CAR T cells with selective inhibitors of nuclear export (SINEs) targeting XPO1 may reduce the risk of tumor escape, although simultaneous use of SINEs and CAR T cells may impair CAR T cell function. Sequential use of SINEs and CAR T cells could potentially enhance the anti-tumor efficacy of CAR T cells.
Article
Biochemistry & Molecular Biology
Jaehun Yoo, Jangmin Lee, Jungwook Kim
Summary: Posttranscriptional modifications of tRNA, especially those within the anticodon, play a crucial role in modulating translational efficiency. In this study, the X-ray crystal structure of Escherichia coli CmoM complexed with tRNA(Ser1) containing 5-carboxymethoxyuridine was determined. The structure revealed conformational changes in both the protein and tRNA at the binding interface, and highlighted the specific molecular interactions between the hypomodified uracil base and the enzyme. Moreover, the structure provided insights into the discriminatory mechanism of the enzyme against non-cognate tRNAs by examining key determinants in the anticodon arm region.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Zheng Liu, Sicai Zhang, Peng Chen, Songhai Tian, Ji Zeng, Kay Perry, Min Dong, Rongsheng Jin
Summary: Toxin B (TcdB) is a key factor in Clostridioides difficile infection (CDI), acting by glucosylating small GTPases in the Rho/Ras families. The recognition mechanism of TcdB towards Rho and R-Ras has been structurally elucidated, with adaptive residue changes in the glucosyltransferase domain (GTD) determining substrate preferences. Mutations disrupting GTPases binding reduce TcdB activity and toxicity, providing insights for therapeutic interventions for CDI.
Article
Multidisciplinary Sciences
Betsegaw Lemma, Di Zhang, Ganga B. Vamisetti, Bryan G. Wentz, Hiroaki Suga, Ashraf Brik, Jacek Lubkowski, David Fushman
Summary: The mechanism of affinity and binding selectivity of cyclic peptides with polyubiquitin chains has been uncovered, along with the requirements for preferential selection of specific structures in longer polyubiquitin chains. These structural insights will guide the development of next-generation cyclic peptides with enhanced anti-cancer activity.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Mingzhen Zhang, Pan Gong, Linhao Ge, Zhaoyang Chang, Xiaofei Cheng, Xueping Zhou, Aiming Wang, Fangfang Li
Summary: The study reveals that XPO1 plays a crucial role in TuMV infection by interacting with NIb to facilitate its translocation to viral replication complexes, as well as mediating the nuclear export of sumoylated NIb and host factors tagged with SUMO3 to suppress plant immunity. Deficiencies of XPO1 in Arabidopsis and Nicotiana benthamiana plants inhibit TuMV replication and infection, highlighting the importance of XPO1 as a host factor in potyvirus infections.
Article
Biochemical Research Methods
Masato Yoshimura, Nai-Chi Chen, Hong-Hsiang Guan, Phimonphan Chuankhayan, Chien-Chih Lin, Atsushi Nakagawa, Chun-Jung Chen
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2020)
Article
Chemistry, Multidisciplinary
Kazushi Fujimoto, Motohiro Fukai, Ryo Urano, Wataru Shinoda, Tetsuya Ishikawa, Katsumi Omagari, Yasuhito Tanaka, Atsushi Nakagawa, Susumu Okazaki
PURE AND APPLIED CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Kayo Imamura, Takanori Matsuura, Atsushi Nakagawa, Shinichi Kitamura, Masami Kusunoki, Takeshi Takaha, Hideaki Unno
Editorial Material
Biochemical Research Methods
Atsushi Nakagawa, John R. Helliwell, Yuriko Yamagata
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yafei Liu, Wai Tuck Soh, Jun-ichi Kishikawa, Mika Hirose, Emi E. Nakayama, Songling Li, Miwa Sasai, Tatsuya Suzuki, Asa Tada, Akemi Arakawa, Sumiko Matsuoka, Kanako Akamatsu, Makoto Matsuda, Chikako Ono, Shiho Torii, Kazuki Kishida, Hui Jin, Wataru Nakai, Noriko Arase, Atsushi Nakagawa, Maki Matsumoto, Yukoh Nakazaki, Yasuhiro Shindo, Masako Kohyama, Keisuke Tomii, Koichiro Ohmura, Shiro Ohshima, Toru Okamoto, Masahiro Yamamoto, Hironori Nakagami, Yoshiharu Matsuura, Atsushi Nakagawa, Takayuki Kato, Masato Okada, Daron M. Standley, Tatsuo Shioda, Hisashi Arase
Summary: The research found that antibodies against different domains of the SARS-CoV-2 spike protein have different effects, with some antibodies inducing an open conformation of the RBD and enhancing the virus infectivity. Structural and mutational analysis revealed the mechanisms of these antibodies, and infectivity-enhancing antibodies were detected at higher levels in severe patients.
Article
Chemistry, Physical
Kazushi Fujimoto, Youhei Yamaguchi, Ryo Urano, Wataru Shinoda, Tetsuya Ishikawa, Katsumi Omagari, Yasuhito Tanaka, Atsushi Nakagawa, Susumu Okazaki
Summary: The study demonstrated that negatively charged substances can approach the HBV capsid by thermal motion, avoiding spikes, and eventually pass through pores to enter the capsid. Chloride ions showed a permeation rate eight times slower than sodium and potassium ions, and were more stable within the capsid.
JOURNAL OF CHEMICAL PHYSICS
(2021)
Article
Biochemistry & Molecular Biology
Takaharu Sakuragi, Ryuta Kanai, Akihisa Tsutsumi, Hirotaka Narita, Eriko Onishi, Kohei Nishino, Takuya Miyazaki, Takeshi Baba, Hidetaka Kosako, Atsushi Nakagawa, Masahide Kikkawa, Chikashi Toyoshima, Shigekazu Nagata
Summary: Xkr8-Basigin is a plasma membrane phospholipid scramblase activated by kinases or caspases. The structure revealed key charged residues essential for its scrambling activity, with phosphatidylcholine binding in a hydrophobic cleft on the surface. The tryptophan residue between the head group of phosphatidylcholine and the extracellular end plays a crucial role in regulating the scramblase activity.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Takafumi Kawai, Hirotaka Narita, Kohtarou Konno, Sharmin Akter, Rizki Tsari Andriani, Hirohide Iwasaki, Shoji Nishikawa, Norihiko Yokoi, Yuko Fukata, Masaki Fukata, Pattama Wiriyasermkul, Pornparn Kongpracha, Shushi Nagamori, Keizo Takao, Tsuyoshi Miyakawa, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Atsushi Nakagawa, Yasushi Okamura
Summary: Voltage-sensing protein TMEM266 has a unique voltage-sensing mechanism and interacts with specific splice variants. The coiled-coil region plays a significant role in forming homodimers, and the cytosolic region at the C-terminal of TMEM266 may bind to various targets. TMEM266 deficiency is associated with behavioral abnormalities.
BIOCHEMICAL JOURNAL
(2022)
Article
Multidisciplinary Sciences
Natsuki Mizutani, Akira Kawanabe, Yuka Jinno, Hirotaka Narita, Tomoko Yonezawa, Atsushi Nakagawa, Yasushi Okamura
Summary: This study investigated the electrochemical coupling in Ciona intestinalis VSP using electrophysiology, fluorometry, and structural modeling. It was found that two hydrophobic residues at the bottom of S4 play a crucial role in the VSD-CCR coupling, with the hydrophobic spine acting as a central hub for translating electrical signals into chemical signals in VSP.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ken-ichi Harada, Kyoko Furuita, Eiki Yamashita, Ken-ichiro Taoka, Hiroyuki Tsuji, Toshimichi Fujiwara, Atsushi Nakagawa, Chojiro Kojima
Summary: In this study, the crystal structure and solution conformation of the free form of St14f protein in potato were investigated. The flexibility of helix I of the 14-3-3 protein was found to play an important role in the recognition of target protein.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Makoto Taniguchi, Akifumi Higashiura, Naoto Kobayashi, Daisuke Kanda, Kakeru Tagata, Ryota Fukunishi, Yasunori Yoshikawa, Emi Kuromatsu, Noriaki Kishida, Yoshinori Kotani, Kentaro Toyoki, Tetsuya Nakamura, Ryoichi Nakatani, Atsushi Nakagawa, Yu Shiratsuchi
Summary: Superparamagnetic Co-Pt nanoparticles were synthesized by soaking Co2+ and PtCl42- into the crystal composed of Pyrococcus furiosus virus-like (PfV) particles. The average diameter of the synthesized particles was approximately 3.6 nm as observed by transmission electron microscopy.
JOURNAL OF PHYSICS AND CHEMISTRY OF SOLIDS
(2022)
Article
Computer Science, Information Systems
Akos Godo, Kota Aoki, Atsushi Nakagawa, Yasushi Yagi
Summary: A neural network-based approach is proposed to accurately and efficiently locate and classify protein residues in electron density maps, showing significant improvement over existing toolkits.
Article
Biochemistry & Molecular Biology
Shoko Shinya, Ritsuko Katahira, Kyoko Furuita, Toshihiko Sugiki, Young-Ho Lee, Yoshikazu Hattori, Kohei Takeshita, Atsushi Nakagawa, Aoi Kokago, Ken-ichi Akagi, Muneki Oouchi, Fumiaki Hayashi, Takanori Kigawa, Midori Takimoto-Kamimura, Toshimichi Fujiwara, Chojiro Kojima
Summary: Fragment-based drug discovery (FBDD) is a powerful tool for drug discovery, but the analysis of protein-compound interactions is challenging due to the low affinity of hit compounds. In this study, a F-19-NMR screening method and an optimized F-19 chemical library were developed to model the complex structure of weak binders and their target proteins. This method was successfully applied to four proteins, including protein kinases and a membrane protein.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Computer Science, Information Systems
Akos Godo, Kota Aoki, Atsushi Nakagawa, Yasushi Yagi
Summary: This study presents a neural network architecture called 3D FC-DenseNet, which assigns amino acid labels to X-ray crystallographic electron density maps without relying on the amino acid sequence of proteins. By creating dedicated data sets and models for different resolutions, the method achieves comparable or better performance than crystallographic toolkits for primary structure assignment, even at low resolutions where current toolkits and human ability fail.
Article
Biochemistry & Molecular Biology
Daisuke Hazama, Yizhen Yin, Yoji Murata, Makoto Matsuda, Takeshi Okamoto, Daisuke Tanaka, Naohiro Terasaka, Jinxuan Zhao, Mariko Sakamoto, Yuka Kakuchi, Yasuyuki Saito, Takenori Kotani, Yoshihiro Nishimura, Atsushi Nakagawa, Hiroaki Suga, Takashi Matozaki
CELL CHEMICAL BIOLOGY
(2020)