Article
Biology
Vincent Van Deuren, Yin-Shan Yang, Karine de Guillen, Cecile Dubois, Catherine Anne Royer, Christian Roumestand, Philippe Barthe
Summary: High-pressure multidimensional NMR has emerged as a powerful tool to describe protein folding landscapes due to its gentle perturbation nature and the multiple probes strategically scattered on the protein structure. The NH amide, C alpha H alpha, and CH3 groups provide similar descriptions of folding pathways with slight differences in thermodynamic parameters, making them valuable for exploring protein conformational landscapes.
Article
Biochemistry & Molecular Biology
Cecile Dubois, Vicente J. Planelles-Herrero, Camille Tillatte-Tripodi, Stephane Delbecq, Lea Mammri, Elena M. Sirkia, Virginie Ropars, Christian Roumestand, Philippe Barthe
Summary: High hydrostatic pressure combined with NMR spectroscopy was used to study the unfolding pathway of the small alpha-helical bundle domain GIPC1-GH2. The unfolding transition was found to be highly cooperative at high temperature, similar to chemical denaturation, while more progressive at low temperature, suggesting a complex folding pathway.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Leonore Novak, Maria Petrosino, Daniele Santorelli, Roberta Chiaraluce, Valerio Consalvi, Alessandra Pasquo, Carlo Travaglini-Allocatelli
Summary: A Phi value analysis was conducted on BRD2(2) to investigate its folding pathway, revealing that the C-terminal region serves as the initial folding nucleus, with the N-terminal region consolidating its structure later in the process. This indicates a hierarchical mechanism of protein folding with non-native interactions playing a significant role.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemical Research Methods
Chad D. Hyer, Hsien-Jung L. Lin, Connor T. Haderlie, Monica Berg, John C. Price
Summary: The structure of a protein defines its function and integrity, and quantifying protein folding stability (PFS) is crucial for understanding disease mechanisms. However, the lack of a user-friendly data processing tool has hindered PFS studies. We present C-Half, a user-friendly software with a graphical interface for calculating PFS, and expect its introduction to promote the usage of PFS in research.
JOURNAL OF PROTEOME RESEARCH
(2023)
Article
Multidisciplinary Sciences
Joseph L. Harman, Patrick N. Reardon, Shawn M. Costello, Gus D. Warren, Sophia R. Phillips, Patrick J. Connor, Susan Marqusee, Michael J. Harms
Summary: This study identified a mutation in S100A9 protein that simultaneously increased its stability and disrupted its natural ability to regulate Toll-like receptor 4. Structural analysis revealed that the mutation distorted the hydrophobic binding surface of the protein, leading to its functional impairment. Bioinformatic analysis further showed that Phe residues at both positions 37 and 63 are rarely found in S100A9 proteins from different organisms, suggesting that avoiding pathological stabilizing interactions constrains the evolution of S100A9.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ruiyue Tan, Margaret Hoare, Kevin A. Welle, Kyle Swovick, Jennifer R. Hryhorenko, Sina Ghaemmaghami
Summary: The folding of proteins during translation while bound to the ribosome is not well understood. This study developed a method using mass spectrometry to measure the stability of nascent polypeptide chains. The results showed that the ribosome significantly influences the stability of the nascent polypeptides, with variations depending on different folding domains and localized charge distributions within the polypeptides. The study suggests that electrostatic interactions between the ribosome and nascent polypeptides play a role in these stability modulations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Federica Agosta, Pietro Cozzini
Summary: Non-covalent intramolecular interactions are crucial for protein folding. Changes in amino acids, pH, or temperature can lead to misfolding or unfolding of proteins, resulting in functional impairment and pathological conditions. The recently implemented HINT scoring function is proposed as a rapid and sensitive method to evaluate destabilization processes. This study evaluates the stability of Transthyretin by generating mutated models under different pH conditions and comparing with experimental data, suggesting that the HINT scoring function can accurately and rapidly predict the effects of structural changes on protein systems.
COMPUTERS IN BIOLOGY AND MEDICINE
(2023)
Article
Biochemical Research Methods
Yesol Sapozhnikov, Jagdish Suresh Patel, F. Marty Ytreberg, Craig R. Miller
Summary: In this study, a statistical framework is developed to quantify the uncertainty of predicted protein stability changes using the computational tool FoldX. It is found that the precision of the model improves significantly when molecular dynamics simulation is incorporated into the FoldX workflow.
BMC BIOINFORMATICS
(2023)
Article
Biochemistry & Molecular Biology
Renan Vergara, Tania Berrocal, Eva Isela Juarez Mejia, Sergio Romero-Romero, Isabel Velazquez-Lopez, Nancy O. Pulido, Haven A. Lopez A. Sanchez, Daniel-Adriano Silva, Miguel Costas, Adela Rodriguez-Romero, Rogelio Rodriguez-Sotres, Alejandro Sosa-Peinado, D. Alejandro Fernandez-Velasco
Summary: This article describes the ligand binding, conformational stability and folding kinetics of the Lysine Arginine Ornithine (LAO) binding protein from Salmonella thiphimurium and constructs corresponding to its two independent domains. The results reveal unexpected behavior of the continuous and discontinuous domains, indicating the crucial role of the continuous domain in nucleating folding.
Article
Biochemistry & Molecular Biology
Maria Conde-Gimenez, Javier Sancho
Summary: Phenylketonuria is an autosomal recessive disorder caused by PAH variants, and one current therapeutic approach is to use pharmacological chaperones to rescue the enzyme's physiological function. This study investigates the folding equilibrium of PAH to develop new pharmacological chaperones for different forms of the disease. The research shows that both urea and thermal-induced denaturation of PAH result in the accumulation of equilibrium unfolding intermediates, indicating potential targets for drug development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Engineering, Environmental
Jiajun Han, Jesse Fu, Jianxian Sun, David Ross Hall, Diwen Yang, Donovan Blatz, Keith Houck, Carla Ng, Jon Doering, Carlie LaLone, Hui Peng
Summary: The study developed a quantitative interspecies thermal shift assay (QITSA) for investigating chemical-protein interactions across species, using liver fatty acid binding protein (L-FABP) as a case study. Results showed that PFOS exhibited the highest binding affinity to human L-FABP, with variations observed in binding affinities among different species. The experimental strategy implemented in this study may have implications for assessing the toxicity of other chemical contaminants in the future.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2021)
Review
Endocrinology & Metabolism
Balamurugan Dhayalan, Deepak Chatterjee, Yen-Shan Chen, Michael A. Weiss
Summary: Analysis of diabetes-associated mutations in the human insulin gene has provided insights into the folding mechanisms of proinsulin, revealing the impact of mutations on pancreatic beta-cell dysfunction and insulin secretion. Studies suggest that conserved residues play a crucial role in folding efficiency and the susceptibility of proinsulin to impaired foldability can contribute to the development of diseases. This highlights the molecular links between biophysical principles and the impact on diseases such as diabetes and obesity.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Wanyue Xu, Jingjie Xu, Caiping Shi, Jing Wu, Huaxia Wang, Wei Wu, Xiangjun Chen, Lidan Hu
Summary: This study identified a novel mutation (Ile82Met) in gamma A-crystallin and investigated its potential molecular mechanism in cataract. The mutation was found to decrease protein stability and increase aggregatory potency under stressful conditions. Furthermore, chemical denaturation affected the unfolding process of gamma A-crystallin.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Biochemistry & Molecular Biology
Paola Turina, Piero Fariselli, Emidio Capriotti
Summary: The study of protein folding is crucial for understanding protein function and the relationship between genetics and phenotypes. K-Pro is a new database that collects experimental kinetic data on monomeric proteins with a two-state folding mechanism. It provides a user-friendly interface for browsing and downloading relevant data.
JOURNAL OF MOLECULAR BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Dina Listov, Rosalie Lipsh-Sokolik, Stephane Rosset, Che Yang, Bruno E. Correia, Sarel Jacob Fleishman
Summary: Recent advances in protein-design methodology have increased reliability and scale, but the success rate in design of functional proteins remains low. Diagnostic and amelioration methods for suboptimal regions in designed proteins can improve the success rate, and using structure prediction methods to flag misfolding regions in enzymes and binders is effective.
Article
Chemistry, Multidisciplinary
Jim-Marcel Knop, Satyajit Patra, Balasubramanian Harish, Catherine A. Royer, Roland Winter
CHEMISTRY-A EUROPEAN JOURNAL
(2018)
Article
Biochemistry & Molecular Biology
Kiran K. Andra, Savanna Dorsey, Catherine A. Royer, Anant K. Menon
JOURNAL OF BIOLOGICAL CHEMISTRY
(2018)
Article
Biochemistry & Molecular Biology
Yi Zhang, Melanie Berghaus, Sean Klein, Kelly Jenkins, Siwen Zhang, Scott A. McCallum, Joel E. Morgan, Roland Winter, Doug Barrick, Catherine A. Royer
JOURNAL OF MOLECULAR BIOLOGY
(2018)
Article
Biochemistry & Molecular Biology
Savanna Dorsey, Sylvain Tollis, Jing Cheng, Labe Black, Stephen Notley, Mike Tyers, Catherine A. Royer
Article
Multidisciplinary Sciences
Kelly A. Jenkins, Martin J. Fossat, Siwen Zhang, Durgesh K. Rai, Sean Klein, Richard Gillilan, Zackary White, Grayson Gerlich, Scott A. McCallum, Roland Winter, Sol M. Gruner, Doug Barrick, Catherine A. Royer
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Multidisciplinary Sciences
Thor C. Moller, Jerome Hottin, Caroline Clerte, Jurriaan M. Zwier, Thierry Durroux, Philippe Rondard, Laurent Prezeau, Catherine A. Royer, Jean-Philippe Pin, Emmanuel Margeat, Julie Kniazeff
SCIENTIFIC REPORTS
(2018)
Article
Biophysics
Siwen Zhang, Yi Zhang, Natalie E. Stenzoski, Junjie Zou, Ivan Peran, Scott A. McCallum, Daniel P. Raleigh, Catherine A. Royer
BIOPHYSICAL JOURNAL
(2019)
Review
Biochemistry & Molecular Biology
Catherine A. Royer
Article
Biophysics
Balasubramanian Harish, Richard E. Gillilan, Junjie Zou, Jinqiu Wang, Daniel P. Raleigh, Catherine A. Royer
Summary: The study reveals that the pressure-unfolded state of the protein is very similar to the unfolded state observed at ambient pressure, demonstrating that pressure perturbation is a powerful approach for observing the unfolded states of proteins under nearly native conditions.
BIOPHYSICAL JOURNAL
(2021)
Article
Biophysics
Balasubramanian Harish, Jinqiu Wang, Eric J. Hayden, Bastian Grabe, Wolf Hiller, Roland Winter, Catherine A. Royer
Summary: Fluorescent RNA aptamers have the potential for routine quantitation and localization of RNA molecules, and can serve as models for understanding biologically active aptamers. Pressure has been shown to be a useful variable in studying RNA folding intermediates.
BIOPHYSICAL JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Daniel R. Colman, Gilles Labesse, Gurla V. T. Swapna, Johanna Stefanakis, Gaetano T. Montelione, Eric S. Boyd, Catherine A. Royer
Summary: Dissimilatory sulfite reductase (DsrAB), an ancient enzyme, plays an important role in linking sulfur and carbon biogeochemical cycles. Through structural and evolutionary analyses, this study provides insights into the conservation of certain structural features in DsrAB and reveals potential allosteric communication pathways between subunits. These findings lay a foundation for future research on the biochemical and structural properties of DsrAB.
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
(2022)
Article
Chemistry, Physical
Siwen Zhang, Scott A. McCallum, Richard E. Gillilan, Jinqiu Wang, Catherine A. Royer
Summary: Given the importance of conformational dynamics in protein function, it is crucial to study the time scales and structures associated with these transitions. High pressure perturbation can help characterize conformational dynamics. Repeat proteins are good models for studying the sequence dependence of protein conformational dynamics. The position of cavities in the protein dictates exchange on different time scales.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemical Research Methods
Luca Mazzei, Rebecca Greene-Cramer, Khushboo Bafna, Aleksandar Jovanovic, Anna De Falco, Thomas B. Acton, Catherine Ann Royer, Stefano Ciurli, Gaetano T. Montelione
Summary: This article presents a protocol for producing 3CLpro protease from SARS-CoV-2 in Escherichia coli, including steps for purification and isotope-enriched samples suitable for NMR studies. The article also describes methods for characterizing 3CLpro using mass spectrometry, X-ray crystallography, heteronuclear NMR, and an enzyme assay. For complete details, please refer to the cited paper.
Article
Biochemistry & Molecular Biology
Catherine A. Royer, Mike Tyers, Sylvain Tollis
Summary: Quantitative characterization of protein abundance and interactions in live cells is crucial for understanding and predicting cellular behavior. This review discusses the advantages and limitations of different fluorescence imaging methods for single-cell determination of protein abundance, localization, interactions, and dynamics. The scanning number and brightness (sN & B) technique and its variation, Raster scanning image correlation spectroscopy (RICS), are highlighted for their ability to accurately quantify protein abundance, stoichiometry, and dynamics by exploiting stochastic noise in small measurement volumes.
CURRENT OPINION IN STRUCTURAL BIOLOGY
(2023)