Article
Multidisciplinary Sciences
Anwar Sadat, Satyam Tiwari, S. Sunidhi, Aseem Chaphalkar, Manisha Kochar, Mudassar Ali, Zainab Zaidi, Akanksha Sharma, Kanika Verma, Kannan Boosi Narayana Rao, Manjul Tripathi, Asmita Ghosh, Deepika Gautam, Atul, Arjun Ray, Koyeli Mapa, Kausik Chakraborty
Summary: The surface charge properties of the GroEL/ES chaperonin cavity, especially the negative charges, play a crucial role in its ability to assist protein folding. However, the negative-charge density varies significantly among different bacterial species and is lowest in eukaryotic GroEL/ES homologs. The chaperoning mechanism of GroEL may have changed during evolution to accommodate different mutations on their substrates.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Evan T. Powers, Lila M. Gierasch
Summary: The article discusses the protein folding problem within cells and emphasizes the deployment of chaperones and degradation enzymes to minimize the impact of misfolded states. It also highlights the importance of the proteostasis network in solving the proteome folding problem.
JOURNAL OF MOLECULAR BIOLOGY
(2021)
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)
Article
Biochemistry & Molecular Biology
Jakub Macosek, Guillaume Mas, Sebastian Hiller
Summary: Molecular chaperones play a key role in bacterial protein homeostasis by facilitating protein folding and providing stability in non-native states.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
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)
Review
Cell Biology
Nicholas J. J. Geraghty, Sandeep Satapathy, Mark R. R. Wilson
Summary: The immune system is crucial for organism protection. Complement and ECs play important roles in maintaining protein homeostasis and controlling immune processes. They may interact with pathogens and immune responses, and influence the development of various diseases.
Article
Multidisciplinary Sciences
Philip To, Yingzi Xia, Sea On Lee, Taylor Devlin, Karen G. Fleming, Stephen D. Fried
Summary: The process of protein folding is complex and important, involving cellular factors and processes. Researchers have developed a new method to monitor the structural changes of Escherichia coli proteins in the cell cytosol and with chaperones. The results show that GroEL can assist in refolding the majority of proteins, while DnaK and GroEL have a similar set of proteins that they refold. Additionally, some proteins are not able to be refolded with any chaperones.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Digvijay Singh, Prajna Tripathi, Rahul Sharma, Sonam Grover, Janendra K. Batra
Summary: The N-terminal domain of Mtb ClpB plays a crucial role in the interaction with its co-partners and in the prevention of aggregation of proteins. The substrate binding pocket identified in this study, comprising of nine amino acid residues forming an alpha-helix, is important for the function of ClpB in repairing and resolubilizing aggregated proteins.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Article
Cell Biology
Vinaya Vishwanathan, Patrick D'Silva
Summary: Congenital Sideroblastic Anemia is a rare genetic disorder characterized by abnormal accumulation of iron in erythrocyte precursors, caused by mitochondrial dysfunction. Mutations in mitochondrial Hsp70 have been identified as potentially leading to the disease, suggesting the loss of chaperone activity is a key factor in its pathophysiology.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nina Kurokawa, Rio Midorikawa, Manami Nakamura, Keiichi Noguchi, Ken Morishima, Rintaro Inoue, Masaaki Sugiyama, Masafumi Yohda
Summary: The study examined the oligomeric structural change of CgHspB1 using sedimentation velocity analytical ultracentrifugation. It was found that at low temperatures, CgHspB1 exists as an 18-mer and is relatively unstable, partially dissociating into smaller oligomers. At elevated temperatures, the 24-mer is more stable and in dynamic equilibrium with the dissociated oligomers in the hexameric unit. Additionally, the disulfide bond between conserved cysteine residues plays a role in stabilizing the hexamers.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Microbiology
Wei He, Gangjin Yu, Tianpeng Li, Ling Bai, Yuanyuan Yang, Zixiao Xue, Yonghao Pang, Dana Reichmann, Sebastian Hiller, Lichun He, Maili Liu, Shu Quan
Summary: Our research demonstrates the role of the periplasmic chaperone Spy in maintaining the homeostasis of certain outer membrane proteins (OMPs). Spy utilizes a unique chaperone mechanism to bind OmpX, allowing it to form a partially folded beta-strand secondary structure in a dynamic exchange of conformations. This mechanism differs from that of other E. coli periplasmic chaperones such as Skp and SurA, highlighting the differences in the mechanisms of ATP-independent chaperones.
Article
Biochemistry & Molecular Biology
Alessia Ruggiero, Han-Gyu Choi, Giovanni Barra, Flavia Squeglia, Young Woo Back, Hwa-Jung Kim, Rita Berisio
Summary: The HtpG(Mtb) protein in tuberculosis vaccines is a dimeric nucleotide-binding protein with antigenic properties. The immune response is mainly elicited by the C-terminal and middle domains of the protein. This information can be used to design more stable, easily produced, and effective vaccine antigens.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Kaushik Bhattacharya, Didier Picard
Summary: The Hsp70 and Hsp90 molecular chaperone systems in eukaryotes are crucial for protein homeostasis under normal and stressed conditions, exhibiting both physical and functional interactions to maintain cellular proteostasis. Co-chaperones like Hop and Sti1 play a key role in facilitating substrate transfer from Hsp70 to Hsp90. Interestingly, while eukaryotes rely on the canonical Hsp70-Hop-Hsp90 ternary chaperone complex for optimal maturation and stability of specific clients, prokaryotes can form a binary chaperone complex without Hop, displaying enhanced protein folding and anti-aggregation activities.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Faustine Henot, Elisa Rioual, Adrien Favier, Pavel Macek, Elodie Crublet, Pierre Josso, Bernhard Brutscher, Matthias Frech, Pierre Gans, Claire Loison, Jerome Boisbouvier
Summary: A metastable excited state in the isolated human HSP90 alpha ATP binding domain has been identified, and its structure has been characterized using solution NMR and mutagenesis. It has been demonstrated that this domain can transiently sample a functionally relevant ATP-lid closed state in solution, which is distant from the ground state. This study provides valuable information for the future design of new therapeutic ligands.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Amrita Dawn, Shashank Deep
Summary: This study successfully transformed a significant portion of misfolded TGF beta 3 into folded form by modulating the cellular protein folding machinery, with the coordination of molecular chaperones and the presence of osmolytes impacting the solubility of TGF beta 3. Additionally, the functionality of soluble TGF beta 3 was confirmed by its binding interaction with its cognate receptor T beta RII, indicating a potential for further research in this area.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biophysics
R. Bryn Fenwick, David Oyen, Henry van den Bedem, H. Jane Dyson, Peter E. Wright
Summary: NMR relaxation dispersion measurements were used to study conformational changes in DHFR on the millisecond-microsecond timescale, generating structural models of alternative conformations using unsigned chemical shift changes. The combination of fragment modeling with sparse chemical shift data successfully characterized a minor conformational state of DHFR sampled on the microsecond-millisecond timescale, showing potential for in silico drug screening and contributing to understanding the role of minor states in biology and molecular evolution.
BIOPHYSICAL JOURNAL
(2021)
Article
Chemistry, Medicinal
Kate A. Stafford, Brandon M. Anderson, Jon Sorenson, Henry van den Bedem
Summary: This paper introduces a deep learning-based approach, AtomNet PoseRanker (ANPR), to improve the quality of docking poses in virtual high-throughput screening (vHTS). Unlike traditional methods, ANPR can handle the dynamic nature of proteins, thus improving the accuracy of docking results.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Chemistry, Medicinal
Xiyu Chen, Sigrid Leyendecker, Henry van den Bedem
Summary: The conformation of a protein affects its function and interaction with ligands, with entropy playing a crucial role. This study presents a method to estimate the vibrational entropy of proteins using kinematic flexibility analysis, providing insights into protein-ligand binding.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Article
Biology
Stephanie A. Wankowicz, Saulo H. de Oliveira, Daniel W. Hogan, Henry van den Bedem, James S. Fraser
Summary: This study measured conformational heterogeneity in a large number of crystallographic datasets and found that binding site residues become more rigid upon ligand binding, while distant residues become more flexible, especially in non-solvent-exposed regions. Additionally, protein flexibility was observed to increase as the number of hydrogen bonds decreases and relative hydrophobicity increases.
Review
Biochemistry & Molecular Biology
Bikash R. Sahoo, James C. A. Bardwell
Summary: Amyloid formation is a misfolding process associated with age-related diseases. Understanding the cellular factors that affect this process is crucial for controlling it. SERF proteins play a role in accelerating polyglutamine amyloid formation and nucleation. The biological functions of SERF proteins, particularly their nucleic acid-binding function and its relationship with their ability to accelerate amyloid formation, are still unclear.
Article
Biochemistry & Molecular Biology
Vishakha Choudhary, Kevin Wu, Zhiyao Zhang, Mark Dulchavsky, Todd Barkman, James C. A. Bardwell, Frederick Stull
Summary: The study reveals that the soil-dwelling bacterium Pseudomonas putida S16 can survive on nicotine as its sole carbon and nitrogen source. The enzymes NicA2 and Pnao, which are members of the flavincontaining amine oxidase family, are shown to be dehydrogenases that use CycN as their electron acceptor.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Kevin Wu, Thomas C. Minshull, Sheena E. Radford, Antonio N. Calabrese, James C. A. Bardwell
Summary: Trigger factor plays a more active role in protein folding by binding to partially folded proteins, preventing non-productive self-association, and facilitating proteins to reach a native-like intermediate state before completing folding and acquiring enzymatic activity upon release.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Bryan B. Guzman, Ahyun Son, Theodore J. Litberg, Zijue Huang, Daniel Dominguez, Scott Horowitz
Summary: This state-of-the-art review explores the interaction between nucleic acids and proteins, specifically focusing on the G-quadruplex structure of RNA and DNA. It discusses how G-quadruplexes influence protein aggregation, proteolysis, phase separation, and protein misfolding diseases, and highlights unanswered questions in this scientific field.
Editorial Material
Biochemistry & Molecular Biology
James C. A. Bardwell
Summary: In this study, Frydman and colleagues successfully visualized the folding process of tubulin by its chaperonin TRiC at near-atomic resolution, shedding light on the mechanism of protein folding.
Article
Chemistry, Multidisciplinary
Guillaume Hoffmann, Madalen Le Gorrec, Emeline Mestdach, Stephen Cusack, Loic Salmon, Malene Ringkjobing Jensen, Andres Palencia
Summary: This study reveals a novel enzyme-independent prodrug activation mechanism by boron-based compounds targeting leucyl-tRNA synthetase. These benzoxaboroles act as prodrugs that activate their bioconversion by forming a specific and reversible inhibition adduct with ATP, AMP, or the terminal adenosine of the tRNALeu. This adenosine-dependent activation mechanism explains the good druglike properties and broad efficacy of benzoxaboroles against different human pathogens.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Sirine Nouri, Julien Boudet, Hiang Dreher-Teo, Frederic H. -T. Allain, Rudi Glockshuber, Loic Salmon, Christoph Giese
Summary: In NMR spectroscopy, residual dipolar couplings (RDCs) are highly accurate probes for investigating biological structure and dynamics. Type 1 pili, derived from bacteria, are introduced as an alternative liquid-crystalline alignment medium for measuring RDCs. By elongating wild-type pili, the medium is made suitable for efficient NMR sample preparation. Additionally, type 1 pili demonstrate compatibility with challenging experimental conditions, making them a valuable alternative to traditional alignment media in NMR studies.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Ahyun Son, Veronica Huizar Cabral, Zijue Huang, Theodore J. Litberg, Scott Horowitz
Summary: Recent research has found that G-quadruplex (G4) nucleic acids are effective in preventing protein aggregation and improving protein folding in Escherichia coli. Through in vitro protein folding experiments, it was discovered that G4s can accelerate protein folding by rescuing kinetically trapped intermediates. Time-course folding experiments in E. coli further showed that G4s primarily enhance protein folding quality instead of preventing protein aggregation. This study suggests that nucleic acids and ATP-independent chaperones may play important roles in determining the folding fate of proteins.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Multidisciplinary
Rohit Roy, Ainan Geng, Honglue Shi, Dawn K. Merriman, Elizabeth A. Dethoff, Loic Salmon, Hashim M. Al-Hashimi
Summary: Understanding the 3D structures and kinetic rates of interconversion of RNA conformations is crucial for studying RNA folding and function. This study developed an approach that combines computational modeling with experimental data to determine the 3D structures, relative abundance, and interconversion rates of RNA subensembles. The approach was applied to HIV-1 TAR and revealed the atomic-level details of sparsely populated RNA excited conformational states. This work provides important insights into the dynamics and structures of RNA conformational substates.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Biochemistry & Molecular Biology
Theodore J. Litberg, Rajesh Kumar Reddy Sannapureddi, Zijue Huang, Ahyun Son, Bharathwaj Sathyamoorthy, Scott Horowitz
Summary: Maintaining a healthy protein folding environment is essential for cellular function. Recently, nucleic acids, especially G-quadruplexes, were found to be effective chaperones for preventing protein aggregation. Through structure-function and NMR analyses, several factors that affect the ability of G-quadruplexes to prevent protein aggregation, such as structural topology, accessibility and dynamics of G-quadruplexes, and their oligomerization state, were identified. Understanding these factors will help elucidate the possible roles of G-quadruplexes in neurodegenerative disease.
Article
Materials Science, Multidisciplinary
Carina Ade, Thais F. Marcelino, Mark Dulchavsky, Kevin Wu, James C. A. Bardwell, Brigitte Stadler
Summary: Extremophile enzymes are valuable in biotechnology and biomedicine due to their ability to survive in harsh environments. Thermoplasma acidophilum histidine ammonia lyase showed promising catalytic activity after acid treatment, and fusion with proteins or co-incubation with chaperones helped it withstand acidic conditions. Encapsulation of the enzyme in a hydrogel microreactor allowed it to maintain over 50% of its enzymatic activity after exposure to simulated gastric and intestinal fluids, showing the potential for advancing oral formulations of biologicals using engineered extremophile proteins and polymer-based encapsulation.
MATERIALS ADVANCES
(2022)