Article
Genetics & Heredity
Delfien Syx, Yoshihiro Ishikawa, Jan Gebauer, Sergei P. Boudko, Brecht Guillemyn, Tim Van Damme, Sanne D'hondt, Sofie Symoens, Sheela Nampoothiri, Douglas B. Gould, Ulrich Baumann, Hans Peter Bachinger, Fransiska Malfait
Summary: Osteogenesis imperfecta is caused by a homozygous p.(R222S) substitution in the HSP47 gene, resulting in significantly reduced affinity of HSP47-R222S for type I collagen and leading to overmodification of type I collagen. Unlike other types of OI, this overmodification is not due to prolonged exposure of collagen to modifying enzymes, as the intracellular folding rate of type I collagen appears to be normal. Abnormal binding of HSP47-R222S results in upregulation and increased binding of molecular chaperones and collagen-modifying enzymes, suggesting a compensatory mechanism for aberrant binding and eventually leading to overmodification of type I collagen chains.
Review
Biochemistry & Molecular Biology
Xinjian Wang, Chengyu Fan, Yanfen Liu, Yan Zou
Summary: The endoplasmic reticulum (ER) and microtubule (MT) network are interconnected and crucial for ER maintenance, MT stability, and various biological processes. ER shaping proteins regulate ER morphology and dynamics, establishing the physical contact structure between ER and MT. Motor proteins and adaptor-linking proteins facilitate bidirectional communication between the two structures. This review summarizes the current understanding of ER-MT interconnection and highlights its importance in maintaining neuronal functions and pathogenesis of neurodegenerative diseases such as Hereditary Spastic Paraplegia (HSP).
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2023)
Review
Biochemistry & Molecular Biology
Shinya Ito, Kazuhiro Nagata
Summary: Collagen, the most abundant protein in mammals, has a unique triple-helical structure formed by Gly-Xaa-Yaa repeats, crucial for its functions such as bone strength and signal transduction. The quality control of collagen biosynthesis in the endoplasmic reticulum is maintained by heat shock protein 47, mutations affecting this process can lead to collagen destabilization and degradation.
ANNUAL REVIEW OF BIOCHEMISTRY, VOL 90, 2021
(2021)
Article
Medicine, General & Internal
Mitchel J. R. Ruigrok, Khaled E. M. El Amasi, Diana J. Leeming, Jannie M. B. Sand, Henderik W. Frijlink, Wouter L. J. Hinrichs, Peter Olinga
Summary: IPF is a chronic lung disease with an urgent need for more effective drugs, with HSP47 identified as a potential therapeutic target. Targeted siRNA therapy against Serpinh1 showed reduction in fibronectin secretion in fibrotic lung slices, indicating a promising approach for fibrosis treatment.
FRONTIERS IN MEDICINE
(2021)
Article
Clinical Neurology
Luis Carlos Tabara, Fatema Al-Salmi, Reza Maroofian, Amna Mohammed Al-Futaisi, Fathiya Al-Murshedi, Joanna Kennedy, Jacob O. Day, Thomas Courtin, Aisha Al-Khayat, Hamid Galedari, Neda Mazaheri, Margherita Protasoni, Mark Johnson, Joseph S. Leslie, Claire G. Salter, Lettie E. Rawlins, James Fasham, Almundher Al-Maawali, Nikol Voutsina, Perrine Charles, Laura Harrold, Boris Keren, Edmund R. S. Kunji, Barbara Vona, Gholamreza Jelodar, Alireza Sedaghat, Gholamreza Shariati, Henry Houlden, Andrew H. Crosby, Julien Prudent, Emma L. Baple
Summary: Hereditary spastic paraplegia (HSP), a genetically diverse neurodegenerative disease, can be classified as pure or complex forms. Biallelic variants in the TMEM63C gene were identified in individuals with HSP and mild intellectual disability. Further analysis showed that TMEM63C plays a role in regulating both endoplasmic reticulum and mitochondrial morphologies.
Article
Biochemistry & Molecular Biology
Hitomi Nakao, Akira Seko, Yukishige Ito, Masafumi Sakono
Summary: This study found that the endoplasmic reticulum protein ERp29 may act as a bridge linking the lectin chaperones calnexin and calreticulin, forming complexes such as CNX-CRT. This not only facilitates the binding of CNX and CRT, but also reveals a new function of ERp29.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Veronik Lachance, Sara-Maude Belanger, Celia Hay, Victoria Le Corvec, Vina Banouvong, Mathieu Lapalme, Khadija Tarmoun, Guillaume Beaucaire, Marc P. Lussier, Said Kourrich
Summary: In recent years, research on the Sigma-1R (S1R) protein has shown its importance in maintaining cellular homeostasis through modulation of calcium and lipid exchange, ER-stress response, and other mechanisms. Many of these processes have been linked to neuroprotective roles, and using S1R agonists to improve these mechanisms has shown benefits in treating brain disorders. This review article explores the subcellular localization and biological activity of S1R within specific compartments, and discusses how dysregulation of these pathways contributes to neurodegenerative diseases, highlighting key binding partners and cellular mechanisms involved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Nadia Garibaldi, Barbara M. Contento, Gabriele Babini, Jacopo Morini, Stella Siciliani, Marco Biggiogera, Mario Raspanti, Joan C. Marini, Antonio Rossi, Antonella Forlino, Roberta Besio
Summary: The chemical chaperone 4-phenylbutyrate (4-PBA) has been shown to improve osteoblast homeostasis and bone matrix quality in osteogenesis imperfecta (OI), indicating its potential as a treatment for OI.
Article
Multidisciplinary Sciences
Gunes Parlakgul, Ana Paula Arruda, Song Pang, Erika Cagampan, Nina Min, Ekin Guney, Grace Yankun Lee, Karen Inouye, Harald F. Hess, C. Shan Xu, Gokhan S. Hotamisligil
Summary: This study reveals the complex structural organization of organelles in liver tissue and highlights the significant alterations in obese mice. The functional importance of these structural changes on cellular and systemic metabolism is also demonstrated.
Article
Plant Sciences
Neeta Lohani, Mohan B. Singh, Prem L. Bhalla
Summary: Increases in extreme temperature events caused by climate change negatively affect agricultural productivity and global food security. New research has found that in high temperatures, oilseed rape anthers undergo rapid transcriptional reprogramming to respond to the unfolded protein response. Additionally, the study found that heat stress can activate the cytosolic heat response network. These findings shed light on the early stress-responsive mechanisms in plant cells.
FRONTIERS IN PLANT SCIENCE
(2022)
Article
Gastroenterology & Hepatology
Samuel C. Buchl, Zachary Hanquier, Andrew J. Haak, Yvonne M. Thomason, Robert C. Huebert, Vijay H. Shah, Jessica L. Maiers
Summary: The study identified TNIK as a key regulator of procollagen I trafficking in vitro and hepatic fibrogenesis in vivo, suggesting that inhibition of TNIK could be a potential therapeutic target for limiting liver fibrosis.
HEPATOLOGY COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Kohta Miura, Riko Katsuki, Shusei Yoshida, Ren Ohta, Taku Tamura
Summary: ERAD is an essential process for maintaining cell function and preventing ER stress. EDEM1 was found to be involved in accelerating the degradation of EGFR via ERAD, highlighting its physiological role in maintaining specific target proteins and providing a potential approach to regulate the expression of clinically important proteins.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Katarzyna Mnich, Shirin Moghaddam, Patrick Browne, Timothy Counihan, Stephen P. Fitzgerald, Kenneth Martin, Ciaran Richardson, Afshin Samali, Adrienne M. Gorman
Summary: ER stress-regulated proteins in blood may serve as diagnostic biomarkers for Parkinson's disease (PD).
MOLECULAR NEUROBIOLOGY
(2023)
Article
Biochemical Research Methods
Tito Cali, Marisa Brini
Summary: Membrane contact sites between organelles play a crucial role in cellular homeostasis and can be quantified using SPLICS sensors in both fixed and living cells.
Review
Cell Biology
Ming Yang, Shilu Luo, Xi Wang, Chenrui Li, Jinfei Yang, Xuejing Zhu, Li Xiao, Lin Sun
Summary: The endoplasmic reticulum (ER) is crucial for maintaining cellular homeostasis, and ER-phagy, a selective form of autophagy, helps remove damaged ER to protect cells from harm caused by excessive ER stress. Many receptor-mediated ER-phagy pathways have been discovered in recent years, highlighting the importance of this newly identified autophagy process in maintaining cellular health.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Hayama Tsutsumi, Yoshitaka Moriwaki, Tohru Terada, Kentaro Shimizu, Kazuo Shin-ya, Yohei Katsuyama, Yasuo Ohnishi
Summary: In this study, we characterized the geranyl pyrophosphate C6-methyltransferase BezA and investigated the molecular basis of its catalytic mechanisms using multiple strategies. The results revealed the important role of E170 as a catalytic base in completing the methylation reaction. Additionally, we successfully altered the substrate specificity by introducing a W210A substitution, resulting in a novel farnesyl pyrophosphate C6-methyltransferase.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Marin Yokomine, Jumpei Morimoto, Yasuhiro Fukuda, Yota Shiratori, Daisuke Kuroda, Takumi Ueda, Koh Takeuchi, Kouhei Tsumoto, Shinsuke Sando
Summary: In this study, oligo(N-methylalanine) (oligo-NMA) is proposed as a peptide-based molecular scaffold with a minimal structure and a high density of functionalizable sites. Oligo-NMA forms a defined shape in water without hydrogen-bonding networks or ring constraints. It can be easily functionalized on the nitrogens and a-carbons. The usefulness of oligo-NMA is demonstrated by the design of protein ligands.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Ryuhei Nagata, Hironori Suemune, Masaya Kobayashi, Tetsuro Shinada, Kazuo Shin-ya, Makoto Nishiyama, Tomoya Hino, Yusuke Sato, Tomohisa Kuzuyama, Shingo Nagano
Summary: This study elucidated the crystal structures of a new subclass of aromatic substrate PTs, and highlighted the essential roles of Ile and Asp residues in interactions with prenyl acceptors. A novel deprotonation mechanism involving a catalytic triad for aromatic substrate PTs was proposed based on structural and mutational analyses.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biotechnology & Applied Microbiology
Ayumu Demachi, Satoshi Ohte, Ryuji Uchida, Kazuo Shin-ya, Taichi Ohshiro, Hiroshi Tomoda, Haruo Ikeda
Summary: The study focused on the key intermediate in scopranone biosynthesis, prescopranone, and elucidated its structure. The results showed that prescopranone is produced through modular polyketide synthesis, and it exhibits inhibitory activity on BMP receptor mutant cell lines.
JOURNAL OF ANTIBIOTICS
(2022)
Article
Biochemistry & Molecular Biology
Koh Takeuchi, Yoshiki Ikeda, Miki Senda, Ayaka Harada, Koji Okuwaki, Kaori Fukuzawa, So Nakagawa, Hong Yang Yu, Lisa Nagase, Misaki Imai, Mika Sasaki, Yu-Hua Lo, Doshun Ito, Natsuki Osaka, Yuki Fujii, Atsuo T. Sasaki, Toshiya Senda
Summary: Unlike most kinases, PI5P4K8 utilizes GTP as a phosphate donor and regulates cell growth under stress. It has evolved GTP responsiveness through the acquisition of a specific recognition motif.
Article
Biochemistry & Molecular Biology
Fumitaka Kudo, Kosuke Kishikawa, Kazuma Tsuboi, Takafusa Kido, Takeo Usui, Junko Hashimoto, Kazuo Shin-ya, Akimasa Miyanaga, Tadashi Eguchi
Summary: In this study, the biosynthetic gene cluster for virustomycin A, an antibiotic produced by Streptomyces graminofaciens A-8890, was identified. The study also demonstrated the exchangeability of the acyltransferase domain between the PKSs involved in FD-891 biosynthesis and the Vsm PKSs. By exchanging the malonyltransferase domain in the loading module of the PKSs, a two-carbon-elongated analog 26-ethyl-FD-891 was successfully produced with potent cytotoxic activity.
Article
Chemistry, Multidisciplinary
Kuga Arima, Satoko Akiyama, Kazuo Shin-ya, Kenichi Matsuda, Toshiyuki Wakimoto
Summary: Heterocycles with N-N bonds are important components of synthetic drugs and natural products, but their biosynthetic logic is poorly understood. Through gene knockouts and biochemical experiments, we have revealed the major steps in actinopyridazinone biosynthesis, including the unprecedented mechanism involving carrier protein-mediated dihydropyridazinone formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Koh Takeuchi, Miki Senda, Yoshiki Ikeda, Koji Okuwaki, Kaori Fukuzawa, So Nakagawa, Mika Sasaki, Atsuo T. Sasaki, Toshiya Senda
Summary: Through 4 billion years of evolution, various mutations have led to the emergence of de novo genes that encode proteins with novel properties essential for cellular functions. However, the molecular processes underlying how a new protein function evolves are largely speculative. Recent evidence suggests that phosphatidylinositol 5-phosphate 4-kinase beta (PI5P4K beta) evolved into a GTP sensor from an ATP-utilizing kinase in mammalian cells through a mutation in its nucleotide base recognition sequence. This evolutionary transition gave rise to GTP sensing activity, which is crucial for cellular metabolism and tumorigenic activity.
Article
Multidisciplinary Sciences
Jun-ichi Sugiyama, Yuji Tokunaga, Mafumi Hishida, Masahito Tanaka, Koh Takeuchi, Daisuke Satoh, Masahiko Imashimizu
Summary: This study investigates the collective dynamics of protein and water molecules in the sub-terahertz frequency region and their influence on the chemical processes in protein-water systems. The results show that sub-terahertz irradiation gradually decreases the dielectric permittivity of the protein solution by reducing the polarization of water molecules. These findings are important for studying hydration-mediated protein functions based on sub-terahertz irradiation.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Masahito Yoshida, Tetsuya Inaba, Yuko Shibuya, Masayuki Igarashi, Hideo Kigoshi
Summary: We have successfully accomplished the total synthesis, structure determination, and biological evaluation of pargamicin A and one of its diastereomers. Two key tripeptide segments were synthesized using a linear peptide elongation process that includes the direct coupling of a poorly nucleophilic piperazic acid derivative. Comparison of the H-1 and C-13 NMR spectra and the antibacterial activity of the natural and synthetic products successfully revealed the absolute configuration of the N-hydroxy-Ile residue of pargamicin A. The biological evaluation suggested that the stereostructure of the cyclic peptide scaffold plays a crucial role in determining the strength of its antibacterial activity.
Article
Multidisciplinary Sciences
Ken-ichi Takayama, Seiji Matsuoka, Shungo Adachi, Teruki Honma, Masahito Yoshida, Takayuki Doi, Kazuo Shin-ya, Minoru Yoshida, Hiroyuki Osada, Satoshi Inoue
Summary: Various cellular activities are regulated by RNA-protein interactions, including lncRNAs. PSF interaction with its target RNAs is critical for hormone therapy resistance in prostate and breast cancers. A high-throughput screening system identified two promising compounds, N-3 and C-65, which inhibited cancer cell growth and induced apoptosis by inhibiting PSF-RNA interaction.
Article
Chemistry, Multidisciplinary
Masahito Yoshida, Yuhi Okoshi, Hideo Kigoshi
Summary: A concise total synthesis of metacridamides A and B was achieved through repetitive vinylogous Mukaiyama aldol reactions and ynamide-mediated macrolactonization. The spectral data of the synthetic products matched those of the natural compounds, leading to the reassessment of the absolute configuration of the C-9 position as S.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biotechnology & Applied Microbiology
Shiina Suzuki, Shun Saito, Yuki Narushima, Shunta Kodani, Noritaka Kagaya, Hikaru Suenaga, Kazuo Shin-ya, Midori A. Arai
Summary: We screened a library of microbial extracts and compounds and identified Pulicatins F and G, as well as cyclopiazonic acid (CPA), as Notch activators. The synthesized Pulicatin F and G showed activation activity, while CPA increased protein levels and mRNA expression of HES1. CPA also inhibited the expression of FLT3, which is known to inhibit apoptosis, and induced apoptosis in HL-60 cells. The Notch activation by CPA was canceled by the addition of FK506, an inhibitor of calcineurin.
JOURNAL OF ANTIBIOTICS
(2023)
Article
Chemistry, Organic
Jungyeon Kim, Hiroka Kobayashi, Marin Yokomine, Yota Shiratori, Takumi Ueda, Koh Takeuchi, Koji Umezawa, Daisuke Kuroda, Kouhei Tsumoto, Jumpei Morimoto, Shinsuke Sando
Summary: This study reports the first design strategy for beta-peptoids, in which all four backbone dihedral angles are rotationally restricted on a per-residue basis. The introduction of a cyclopentane constraint realized the preorganized monomer structure and led to a beta-peptoid with a stable twisted strand shape.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Abhinav Dubey, Thibault Viennet, Sandeep Chhabra, Koh Takeuchi, Hee-Chan Seo, Wolfgang Bermel, Dominique P. Frueh, Haribabu Arthanari
Summary: Intrinsically disordered regions (IDRs) of proteins play critical roles in the regulation of biological processes but are challenging to study structurally. This study improves the methodology of analyzing IDRs using nuclear magnetic resonance (NMR) by using transverse relaxation optimized spectroscopy (TROSY) at higher magnetic fields and physiological salt concentrations. The new methods have been successfully applied to assign large disordered regions with low sequence complexity.
CHEMICAL COMMUNICATIONS
(2022)
