Article
Chemistry, Physical
Mohd Younus Bhat, Irfan Mir, Laishram Rajendrakumar Singh, Mahboobul Hussain, Tanveer Ali Dar
Summary: Intrinsically disordered proteins (IDPs) play important roles in cellular processes and disease processes, and trehalose affects the structural-functional elasticity of IDPs.
JOURNAL OF MOLECULAR LIQUIDS
(2023)
Review
Biochemistry & Molecular Biology
Owen Michael Morris, James Hilary Torpey, Rivka Leah Isaacson
Summary: This review evaluates the anatomy of intrinsically disordered proteins (IDPs) and how their intrinsic properties allow for diversity and different modes of interaction. It also provides a detailed overview of the types of disordered domains and the kinetic and thermodynamic principles governing their formation, with reference to a recent example.
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
Chemistry, Multidisciplinary
Hanping Wang, Ruoyao Xiong, Luhua Lai
Summary: Intrinsically disordered proteins (IDPs) are proteins without well-defined structures under physiological conditions, but they play important biological functions. They can form fuzzy complexes, contribute to the formation of membraneless organelles, and serve as hubs in protein-protein interaction networks. Targeting IDPs for drug design is challenging due to their highly dynamic structures and fuzzy interactions. However, turning IDPs into druggable targets opens up opportunities for novel drug discovery. Integrative structural biology approaches have been used to uncover the dynamic structures and interactions of IDPs. Several IDP-targeting drugs have advanced into clinical trials, and new computational methods are being developed for efficient discovery and optimization of specific and potent ligands for IDPs. Understanding the dynamic structures and interactions of IDPs is crucial for drug development.
WILEY INTERDISCIPLINARY REVIEWS-COMPUTATIONAL MOLECULAR SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Vladimir N. Uversky, Prakash Kulkarni
Summary: Intrinsic disorder has revolutionized modern protein science, challenging traditional lock-and-key model and paving the way for a new understanding of protein structure-function relationship. The discovery of protein intrinsic disorder phenomenon was a gradual process, where previous discoveries laid the foundation for a paradigm shift in the field.
BIOPHYSICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Thinh D. N. Luong, Suhani Nagpal, Mourad Sadqi, Victor Munoz
Summary: This article introduces a method called "Molecular LEGO" that allows for the dissection of conformational landscapes of unbound intrinsically disordered proteins (IDPs) and provides insights into the functional mechanisms of these proteins. The method was applied to the protein NCBD and revealed specific energetic biases and conformational rheostatic behavior in NCBD's folding landscape, which are likely crucial for its function as a transcriptional coactivator.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Francesca Malagrino, Awa Diop, Livia Pagano, Caterina Nardella, Angelo Toto, Stefano Gianni
Summary: This article focuses on the mechanisms of induced folding in intrinsically disordered proteins (IDPs) upon binding to physiological ligands. The article first describes the general features of the reaction, then discusses some of the most remarkable findings obtained from protein engineering and kinetic studies, and finally offers a critical view on the relationship between structural heterogeneity and inherent frustration in IDPs.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jaka Kragelj, Rania Dumarieh, Yiling Xiao, Kendra K. K. Frederick
Summary: Frozen proteins at cryogenic temperatures can provide detailed conformational restraints for DNP MAS NMR studies. Using peak shapes, conformational features of individual conformers in the ensemble can be assigned through simulation. This has important implications for studying proteins with intrinsically disordered regions in living cells.
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
Biochemistry & Molecular Biology
Jaka Kragelj, Thibault Orand, Elise Delaforge, Laura Tengo, Martin Blackledge, Andres Palencia, Malene Ringkjobing Jensen
Summary: Intrinsically disordered proteins (IDPs) can form promiscuous interactions with their protein targets, facilitated by folding-upon-binding into different conformations. Specific surface properties of the kinases p38 alpha and JNK1 dictate the bound conformation of the regulatory domain MKK4, with enthalpy-entropy compensation playing a major role in maintaining comparable binding affinities towards the two kinases.
Article
Biochemistry & Molecular Biology
San Hadzi, Jurij Lah
Summary: Intrinsically disordered proteins (IDPs) are common in eukaryotic proteomes and can acquire defined conformations upon binding globular targets. The folding penalty of IDPs in alpha-helical binding motifs has been estimated to be around +2.0 kcal/mol, with a range of 0.7 to 3.5 kcal/mol. Pre-folding and target-bound IDP dynamics reduce the folding cost by approximately half. Understanding the role of folding penalty in IDP-target interactions and estimating this quantity can aid in the design of inhibitors for IDP-target interactions.
Article
Chemistry, Physical
Adam K. Sieradzan, Anatolii Korneev, Alexander Begun, Khatuna Kachlishvili, Harold A. Scheraga, Alexander Molochkov, Patrick Senet, Antti J. Niemi, Gia G. Maisuradze
Summary: The study investigates the principles and key residues involved in inducing the folding of an intrinsically disordered protein through multisite phosphorylation. Analysis of experimental structures reveals that kinks can identify important phosphorylated sites and the reasons behind the weak stability of the folded state.
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2021)
Review
Chemistry, Multidisciplinary
Pablo G. Argudo, Juan J. Giner-Casares
Summary: Proteins and peptide fragments play a crucial role in self-assembly for nanostructures, with intrinsically disordered proteins and protein regions showing significant biological activity. Experimental techniques and computational modeling procedures are used for characterization, leading to a wide variety of nanostructures and promising performance in biotechnological applications. Exciting possibilities for IDPs and IDRs in nanotechnology with relevant biological applications are demonstrated.
NANOSCALE ADVANCES
(2021)
Article
Biochemistry & Molecular Biology
Ben M. Smith, Pamela J. E. Rowling, Christopher M. Dobson, Laura S. Itzhaki
Summary: The study investigates the interaction between beta-catenin and TCF7L2, revealing the kinetic characteristics through a fluorescence reporter system and mutagenesis analysis. The results suggest a complex two-site avidity mechanism of binding, with the involvement of transient contacts and alternative dissociation pathways. The study provides insights into the molecular recognition of a long intrinsically disordered region with an elongated repeat-protein surface, involving parallel routes and sequential steps.
Review
Chemistry, Multidisciplinary
Matti Mar, Kateryna Nitsenko, Petur O. Heidarsson
Summary: Eukaryotic transcription factors play a crucial role in integrating molecular feedback and regulating gene expression. They consist of structured DNA-binding domains and long intrinsically disordered regions (IDRs). The dynamic multifunctionality of IDRs is essential for their functions in genome regulation. This review analyzes the chemical features of TF IDRs and their involvement in protein interactions, DNA binding, chromatin opening, and phase separation. Suggestions are given for future research to integrate experiments and simulations in understanding TF functions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Biochemistry & Molecular Biology
Pamela L. Mosley, Kyle G. Daniels, Terrence G. Oas
Meeting Abstract
Biophysics
Yang Qi, Jeffrey W. Martin, Anthony Yan, Francois Thelot, Bruce R. Donald, Terrence G. Oas
BIOPHYSICAL JOURNAL
(2015)
Article
Multidisciplinary Sciences
Kyle G. Daniels, Yang Suo, Terrence G. Oas
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Article
Multidisciplinary Sciences
Lindsay N. Deis, Qinglin Wu, You Wang, Yang Qi, Kyle G. Daniels, Pei Zhou, Terrence G. Oas
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2015)
Meeting Abstract
Biophysics
Robert Jefferson, Yu-Chu Chang, Eitan Lerner, Shimon Weiss, James Bowie
BIOPHYSICAL JOURNAL
(2016)
Article
Biochemistry & Molecular Biology
Riddhi Shah, Tomoo Ohashi, Harold P. Erickson, Terrence G. Oas
JOURNAL OF BIOLOGICAL CHEMISTRY
(2017)
Article
Biochemistry & Molecular Biology
Yang Qi, Jeffrey W. Martin, Adam W. Barb, Francois Thelot, Anthony K. Yan, Bruce R. Donald, Terrence G. Oas
JOURNAL OF MOLECULAR BIOLOGY
(2018)
Article
Chemistry, Multidisciplinary
Nicole I. Orlovsky, Hashim M. Al-Hashimi, Terrence G. Oas
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2020)
Article
Infectious Diseases
Shiuh-Bin Fang, Tsai-Ling Yang Lauderdale, Chih-Hung Huang, Pei-Ru Chang, Yuan-Hung Wang, Katsumi Shigemura, Ying-Hsiu Lin, Wei-Chiao Chang, Ke-Chuan Wang, Tzu-Wen Huang, Yu-Chu Chang
Summary: This study analyzed the genetic diversity of ciprofloxacin nonsusceptibility in nontyphoidal Salmonella and found that QRDR mutations were more common than PMQR genes among the isolates. Both PMQR genes and QRDR mutations were positively correlated with CIP MICs, with double mutations in gyrA and parC determining high CIP resistance.
Article
Health Care Sciences & Services
Wen-Jing Hsu, Cheng-Hsun Chen, Yu-Chu Chang, Chia-Hsiung Cheng, Ying-Huei TsaI, Cheng-Wei Lin
Summary: Elevated expression of PRMT1 was found to be associated with therapeutic sensitivity to the PARP inhibitor olaparib in TNBC cells, particularly those with higher PRMT1 and MYC signature. PRMT1 was shown to modulate DNA repair by regulating c-Myc signaling, highlighting the PRMT1/c-Myc network as a potential therapeutic target in patients with TNBC.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Multidisciplinary Sciences
Ching-Han Lee, Yi-Yun Lee, Yu-Chu Chang, Wen-Li Pon, Sue-Ping Lee, Niaz Wali, Takehito Nakazawa, Yoichi Honda, Jiun-Jie Shie, Yen-Ping Hsueh
Summary: The carnivorous mushroom Pleurotus ostreatus paralyzes and kills its nematode prey using an unknown toxin. It was found that small lollipop-shaped structures called toxocysts on the fungal hyphae are responsible for the nematicidal activity, and a volatile ketone called 3-octanone was detected in these toxocysts. Further experiments showed that treating Caenorhabditis elegans with 3-octanone resulted in rapid paralysis, calcium influx, and neuronal cell death similar to the effects of fungal contact. The ketone disrupts cell membrane integrity, leading to calcium influx and cell death throughout the organism.
Article
Chemistry, Inorganic & Nuclear
Sean Gao, Joanna X. Campbell, Terrence G. Oas, Katherine J. Franz
Summary: In this study, the binding of Hist5 to Zn2+ was investigated using isothermal titration calorimetry. It was found that Hist5 can bind to Zn2+ and this binding is both enthalpically and entropically favorable. The stoichiometry of Zn:Hist5 binding increased from 1:1 to 2:1 with increasing temperature.
INORGANIC CHEMISTRY
(2023)
Article
Infectious Diseases
Yuarn-Jang Lee, Yu-Chu Chang, I-Hui Lee, Kuo-Hao Ho, Shiuh-Bin Fang, Tsai -Ling Lauderdale, Ting-Wen Chen, Ku-Chung Chen, Chih-Hung Huang, Tzu-Wen Huang
Summary: This study provides comprehensive genomic epidemiology of antimicrobial resistance in Nontyphoidal Salmonella (NTS). The results show that the dynamic movement of cephalosporinase genes mediated by IS 26 in NTS is of great concern.
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
(2023)
Article
Biochemistry & Molecular Biology
Wei-Chun Huang, Wai-Ting Chen, Yueh-Chen Chen, Shiuh-Bin Fang, Tzu-Wen Huang, Pei-Ru Chang, Yu-Chu Chang
Summary: Protein oligomerization is crucial for the pathogenesis of Salmonella Typhimurium. YqiC forms a homotrimer and its mutations result in reduced colonization and invasion to host cells. It interacts with subunits of the electron transport chain and ATP synthase, suggesting its role in energy modulation and virulence factor assembly.
Article
Cell Biology
Hung-Hao Fan, Shiuh-Bin Fang, Yu-Chu Chang, Sheng-Tung Huang, Chih-Hung Huang, Pei-Ru Chang, Wei-Chiao Chang, Lauderdale Tsai-Ling Yang, Pei-Chun Lin, Hung-Yen Cheng
Summary: The study revealed that the gene yqiC plays a crucial role in the interactions between Salmonella and host cells, regulating the expression of multiple key genes involved in bacterial virulence, metabolism, and other aspects.
JOURNAL OF BIOMEDICAL SCIENCE
(2022)