Article
Biochemical Research Methods
Qi Liu, Chih-Yuan Hsu, Jia Li, Yu Shyr
Summary: This study developed a statistical method for examining dysregulated ligand-receptor interactions in different conditions, and successfully applied it to the study of important diseases such as COVID-19 infection and pulmonary fibrosis.
Review
Cell Biology
Debora Bencivenga, Emanuela Stampone, Domenico Roberti, Fulvio Della Ragione, Adriana Borriello
Summary: p27(Kip1) plays a crucial role in cell cycle regulation, with additional functions in cell motility, differentiation, apoptosis, and other processes. Its activities are modulated by factors such as level, localization, and post-translational modifications.
Article
Multidisciplinary Sciences
Gerard Duart, Assaf Elazar, Jonathan Y. Weinstein, Laura Gadea-Salom, Juan Ortiz-Mateu, Sarel J. Fleishman, Ismael Mingarro, Luis Martinez-Gil
Summary: Several methods have been developed to explore protein-protein interactions, but there is a need for more research on targeting transmembrane domains (TMDs). This study developed a computational approach to design sequences that can modulate protein-protein interactions in the membrane, and successfully applied it to BclxL. The findings enhance our understanding of protein-protein interactions in membranes and may lead to the development of inhibitors targeting TMD interactions.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Francesco A. Aprile, Piero Andrea Temussi, Annalisa Pastore
Summary: Protein misfolding is a key topic in biology and medicine, influencing fundamental processes and diseases. This review discusses the evolution of the field, focusing on intrinsically unstructured regions and the potential biological significance of misfolding. The review highlights the importance of both structured and unstructured regions in protein aggregation behavior and suggests a more comprehensive evaluation of aggregation mechanisms.
Article
Chemistry, Multidisciplinary
Steffen Luedeke, Philipp Lohner, Lara G. Stuehn, Martin U. Betschart, Matthias C. Huber, Andreas Schreiber, Stefan M. Schiller
Summary: Research has shown that coacervation of Elastin-like proteins occurs sharply when a certain number of repeat units has acquired beta-turn conformation, which is retained even after polypeptide assembly. This conformational threshold may have implications for other protein assembly processes and the design of protein-based smart materials.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Sandeep K. N. Mulukala, Vaishnavi Kambhampati, Abrar H. Qadri, Anil K. Pasupulati
Summary: Vertebrate kidneys play a crucial role in maintaining homeostasis through electrolyte regulation, acid-base balance, and removal of toxic metabolites. The study focuses on the distribution and evolutionary insights of essential SD proteins across organisms with available genome sequences. The findings highlight differences in protein distribution and structural domains between invertebrates and vertebrates, shedding light on the evolutionary trends of these proteins.
Review
Biochemistry & Molecular Biology
Rakesh Trivedi, Hampapathalu Adimurthy Nagarajaram
Summary: This review discusses different aspects of disordered proteins and protein regions, as well as the experimental and computational methods used to characterize them. Additionally, the role of disordered proteins in diseases and their potential as drug targets are explored.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
H. Jane Dyson
Summary: Viruses infect all kingdoms of life and employ disordered proteins to accomplish various functions. Disordered proteins have been discovered in almost all viruses studied, regardless of the viral genome composition or the viral capsid configuration. This review presents a collection of stories illustrating the diverse functions of disordered proteins in viruses, providing a survey of the field's expansion.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Rajkama, Nisal, P. Jitendra, Agata, Susan, Geoff, W. Aaron, J. Anita, Namita Roy, K. Naba
Summary: This study reveals the impact of crowding on the dynamic conformation of intrinsically disordered proteins (IDPs). Through experimental methods and model construction, researchers found that crowding can induce specific conformational changes in IDPs. This study is of great importance for a better understanding of the interactions and structural dynamics of IDPs in crowded environments.
Article
Biochemistry & Molecular Biology
Carson C. Cole, Mikita Misiura, Sarah A. H. Hulgan, Caroline M. Peterson, Joseph W. Williams III, Anatoly B. Kolomeisky, Jeffrey D. Hartgerink
Summary: Cation-pi interactions play a significant role in stabilizing globular proteins, but their role in collagen triple helices is not well understood. This study investigates the effects of pairwise amino acid interactions between cationic and aromatic residues in both axial and lateral relationships.
Article
Biochemistry & Molecular Biology
Kanin Wichapong, Carlos Silvestre-Roig, Quinte Braster, Ariane Schumski, Oliver Soehnlein, Gerry A. F. Nicolaes
Summary: Research has shown that targeting intrinsically disordered proteins and protein regions is a feasible and emerging strategy in drug discovery. By utilizing structure-based methods, peptidic inhibitors have been successfully developed to inhibit specific proteins, which can prevent cell death and reduce the progression of atherosclerosis.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Review
Biotechnology & Applied Microbiology
Victor Alfonso Solarte David, Viviana Raquel Guiza-Argueello, Martha L. Arango-Rodriguez, Claudia L. Sossa, Silvia M. Becerra-Bayona
Summary: The absence or damage of tissue is a major cause of diseases, and novel therapeutic alternatives aim to recover lost functions through tissue regeneration. Chronic cutaneous lesions are common wounds that require regenerative medicine and tissue engineering interventions to develop bioactive medical products for proper healing and prevention of complications. The coordination of cells, extracellular matrix (ECM), and biomolecules is crucial in tissue repair and regeneration, with ECM acting as a biological platform for their interactions. Tissue engineering utilizes synthetic polymers and decellularized tissues to mimic native ECM and provide necessary functionalities for cell differentiation.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Gozde Kibar, Martin Vingron
Summary: Protein-protein interactions (PPIs) are crucial for molecular processes, but the mechanisms of molecular recognition between interacting proteins are poorly understood, making it challenging to predict interactions from sequence. This study proposes a new method using intrinsically disordered regions (IDRs) to tackle this challenge. Using IDR sequences, the researchers predicted PPIs in candidate proteins and divided the prediction problem into subproblems, adapting appropriate strategies. The findings highlight the importance of defining problem type and suggest that accounting for IDRs can aid in predicting features of the intrinsically disordered protein interaction network, accelerating efforts to understand the eukaryotic PPI network.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Jaime Santos, Irantzu Pallares, Valentin Iglesias, Salvador Ventura
Summary: The prevalence of cryptic amyloidogenic regions (CARs) of polar nature in intrinsically disordered regions (IDRs) has been explored. CARs are associated with protein function and interactions, but also carry a risk of malfunction. The existence of ancestral CARs may have evolved into functional interacting regions, playing a significant role in protein evolution at the origins of life.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2021)
Article
Multidisciplinary Sciences
Qi Xing, Mojtaba Parvizi, Manuela Lopera Higuita, Leigh G. Griffiths
Summary: The study found that human mesenchymal stem cells migrated faster on the serous surface than on the fibrous surface, potentially due to increased expression of integrin alpha (3) and alpha (11). Blockade of integrin alpha (3)beta (1) inhibited early hMSC migration on the serous side, while blockade of alpha (11)beta (1) inhibited later hMSC migration.
SCIENTIFIC REPORTS
(2021)
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
Biochemistry & Molecular Biology
Takeru Sagae, Mariko Yokogawa, Ryoichi Sawazaki, Yuichiro Ishii, Nao Hosoda, Shin-ichi Hoshino, Shunsuke Imai, Ichio Shimada, Masanori Osawa
Summary: This study investigated the functional mechanisms of Paip2A in translation repression. The findings reveal that Paip2A can bind to the poly(A)-binding interfaces of PABPC1’s RRM2 and RRM3 regions and effectively dissociate PABPC1 from poly(A). These insights may contribute to the development of novel anticancer and antiviral drugs.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemical Research Methods
Takumi Ueda, Shunsuke Imai, Ichio Shimada
Summary: GPCRs are important receptors for neurotransmitters and hormones, and they are targeted by a significant number of modern drugs. Although the number of GPCR crystal structures has increased rapidly, they alone cannot fully explain the key features of GPCR signaling. Recent studies have shown that GPCRs are structurally dynamic and can adopt multiple conformations. NMR methods provide valuable insights into the dynamics of GPCRs in solution, despite the challenges posed by their instability and large molecular weights.
JOURNAL OF MAGNETIC RESONANCE
(2022)
Article
Multidisciplinary Sciences
Shun Kaneko, Shunsuke Imai, Nobuaki Asao, Yutaka Kofuku, Takumi Ueda, Ichio Shimada
Summary: This study reveals a novel mechanism of GPCR activation and the potential of allosteric modulators to enhance GPCR activity. The use of solution NMR analysis provides insights into the structural changes and equilibrium of GPCRs, shedding light on the rational development of next-generation GPCR-targeting therapeutics.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Yoshimitsu Itoh, Shuo Chen, Ryota Hirahara, Takeshi Konda, Tsubasa Aoki, Takumi Ueda, Ichio Shimada, James J. Cannon, Cheng Shao, Junichiro Shiomi, Kazuhito Tabata, Hiroyuki Noji, Kohei Sato, Takuzo Aida
Summary: This study reports a novel fluorous nanochannel that exhibits a water permeation flux two orders of magnitude higher than that of aquaporins and carbon nanotubes. The hydrophobic interior surface of this nanochannel provides a powerful electrostatic barrier, resulting in nearly perfect salt reflectance. Hence, it holds significant potential for applications in desalination.
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
Wenchao Zhu, Shiori Takeuchi, Shosei Imai, Tohru Terada, Takumi Ueda, Yusuke Nasu, Takuya Terai, Robert E. Campbell
Summary: Molecular fluorescent indicators based on chemigenetic combination of synthetic ion-recognition motifs and protein-based fluorophores are versatile tools for dynamic imaging of biological systems. This design enables the development of chemigenetic indicators with ion or molecular specificities that have not been realized with fully protein-based indicators.
NATURE CHEMICAL BIOLOGY
(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
Multidisciplinary Sciences
Yuki Hosono, Satoshi Uchida, Moe Shinkai, Chad E. Townsend, Colin N. Kelly, Matthew R. Naylor, Hsiau-Wei Lee, Kayoko Kanamitsu, Mayumi Ishii, Ryosuke Ueki, Takumi Ueda, Koh Takeuchi, Masatake Sugita, Yutaka Akiyama, Scott R. Lokey, Jumpei Morimoto, Shinsuke Sando
Summary: Naturally occurring peptides with high membrane permeability usually have ester bonds on their backbones. This study evaluated the effect of amide-to-ester substitutions on the membrane permeability of cyclic peptides and found that this substitution is effective in improving membrane permeability. The findings provide insights into the development of membrane-permeable peptides through appropriate utilization of amide-to-ester substitutions.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Yugo Shimizu, Tomoki Yonezawa, Yu Bao, Junichi Sakamoto, Mariko Yokogawa, Toshio Furuya, Masanori Osawa, Kazuyoshi Ikeda
Summary: We improved the hit rate against a protein-protein interaction target by combining a library of medium-sized molecules with iterative screening using multiple ligand-based machine learning algorithms. Inhibition assays using a PPI target, Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 (Keap1/Nrf2), demonstrated that a deep neural network model based on the first-round assay data achieved the highest hit rate of 27.3%. As a result of using these models, we identified novel active and non-flat compounds that were not present in public datasets, expanding the chemical space.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Yuko Tsuchiya, Tomoki Yonezawa, Yu Yamamori, Hiroko Inoura, Masanori Osawa, Kazuyoshi Ikeda, Kentaro Tomii
Summary: This article introduces the PoSSuM database, which can be used to identify similar binding pockets in proteins, and its drug search feature can investigate the diversity of ligands and receptors in these pockets. In addition, two new databases are introduced: PoSSuMAg for studying antibody-antigen interactions, and PoSSuMAF for simplifying the exploration of putative pockets in AlphaFold human protein models.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(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)
