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
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
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)
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
Multidisciplinary Sciences
Kobe Janssen, Filip Claes, Dido Van de Velde, Vanessa L. Wehbi, Bert Houben, Yulia Lampi, Mieke Nys, Laleh Khodaparast, Ladan Khodaparast, Nikolaos Louros, Rob van der Kant, Joffre Verniers, Teresa Garcia, Meine Ramakers, Katerina Konstantoulea, Katerina Maragkou, Ramon Duran-Romana, Monica Musteanu, Mariano Barbacid, Bernard Scorneaux, Els Beirnaert, Joost Schymkowitz, Frederic Rousseau
Summary: Mutant KRAS is a challenging target for classical small molecule drugs, but this study shows that its misfolding can be induced by synthetic peptides derived from specific regions of the oncoprotein. These peptides were able to inhibit the function of mutant KRAS and showed antiproliferative activity against cancer cells. The findings provide proof-of-concept for exploiting the intrinsic misfolding propensity of KRAS as a therapeutic strategy.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Yovana Cabrera, Ganeko Bernardo-Seisdedos, Leire Dublang, David Albesa-Jove, Natalia Orozco, Ana Rosa Viguera, Oscar Millet, Arturo Muga, Fernando Moro
Summary: This study reveals the role of Apg2 in regulating the activity of human Hsc70, and its C-terminal extension acts as a fine-tuner of substrate remodeling ability in the chaperone system.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biology
Rumi Mikami, Shunsuke Tsukagoshi, Kenta Arai
Summary: Protein folding is a crucial process in determining the overall efficiency of protein synthesis. An artificial folding catalyst, behaving like protein disulfide isomerase (PDI), is essential for promoting correct folding and avoiding misfolding.
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)
Article
Biochemistry & Molecular Biology
Gabriel Wright, Anabel Rodriguez, Jun Li, Tijana Milenkovic, Scott J. Emrich, Patricia L. Clark
Summary: Research has shown that synonymous codon usage can affect various mechanisms related to protein production, especially in co-translational protein folding. Conservation of synonymous codon usage patterns across evolution highlights the potential benefits of matching codon usage patterns from the original organism in heterologous gene expression.
Article
Biotechnology & Applied Microbiology
Gayathri Ravitchandirane, Sheetal Bandhu, Tapan K. Chaudhuri
Summary: This study investigates how the modulation of physiological stimuli and process conditions can increase the solubility and activity of recombinant proteins in E. coli cells. The results show that the presence of exogenous molecular chaperones and osmolytes, as well as the modulation of temperature and inducer concentrations, can enhance the folding of soluble aggregates and improve the functional protein molecules in the cells. The co-expression of GroEL/ES not only aids in protein folding, but also reduces cellular stress caused by aggregation-prone recombinant protein expression.
MICROBIAL CELL FACTORIES
(2022)
Article
Biochemistry & Molecular Biology
Eshita Das, Shivcharan Prasad, Ipsita Roy
Summary: Peptidyl prolyl isomerases play a key role in accelerating protein folding, with larger multi-domain proteins having additional functions beyond isomerization. Yeast Fpr1 exhibits characteristics of a general chaperone in the proteostasis network, reducing protein aggregation and improving cell survival. Overexpression of Fpr1 protects cells against thermal shock, suggesting potential therapeutic implications in disease conditions.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Review
Biochemistry & Molecular Biology
Hideki Taguchi, Ayumi Koike-Takeshita
Summary: Protein folding can be hindered by protein aggregation, but this can be prevented by chaperones in the cell. The bacterial chaperonin GroEL forms complexes with its cochaperonin GroES to facilitate protein folding. Recent studies have identified numerous GroE-dependent clients, shedding light on the role of chaperonins in protein folding and evolution.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Chemistry, Physical
Wenbo Zhang, Mingwei Liu, Lanlan Yu, Shanshan Mo, Zhun Deng, Shuli Liu, Yanlian Yang, Chen Wang, Chenxuan Wang
Summary: This study demonstrates the contribution of various noncovalent interactions to supramolecular assembly by investigating the self-assembly of peptides.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2022)
Article
Multidisciplinary Sciences
Dimitra Panagaki, Jacob T. Croft, Katharina Keuenhof, Lisa Larsson Berglund, Stefanie Andersson, Verena Kohler, Sabrina Buttner, Markus J. Tamas, Thomas Nystrom, Richard Neutze, Johanna L. Hoog
Summary: Nuclear envelope budding (NEB) is an alternative pathway for nucleocytoplasmic communication that is evolutionarily conserved from early protists to human cells. In yeast cells, NEB events occur more frequently under stress conditions such as heat shock, exposure to harmful chemicals, and inhibition of the proteasome. NEB may play a role in aiding the transport of protein aggregates across the nuclear envelope, particularly in response to protein misfolding and heat shock.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Microbiology
Esin Isik, Cigdem Balkan, Vivien Karl, Huseyin Caglar Karakaya, Sansan Hua, Sebastien Rauch, Markus J. Tamas, Ahmet Koc
Summary: This study identified multiple genes contributing to arsenic resistance in yeast through overexpression. The researchers revealed different resistance mechanisms by exploring the effects of gene overexpression on cell growth, intracellular arsenic, and protein aggregation levels.
Review
Biochemistry & Molecular Biology
Declan R. Creamer, Simon J. Hubbard, Mark P. Ashe, Chris M. Grant
Summary: Eukaryotic cells have developed a complex circuitry of signalling molecules to monitor changes in their environments. The cAMP/PKA pathway is an important glucose sensing circuit in yeast, and PKA activity regulates various processes in yeast growth. However, the molecular basis of PKA signalling specificity is poorly understood.
Article
Genetics & Heredity
Karl Persson, Simon Stenberg, Markus J. Tamas, Jonas Warringer
Summary: This study utilized a high-throughput method to track the adaptive evolution of cell populations and found that the preadaptation fitness of gene knockouts accurately predicts their adaptation to selection pressures, indicating a limited role for dedicated evolvability gene functions. Additionally, global epistasis was identified as a factor influencing adaptation.
G3-GENES GENOMES GENETICS
(2022)
Article
Biology
Andrew Ck Wu, Claudia Vivori, Harshil Patel, Theodora Sideri, Fabien Moretto, Folkert J. van Werven
Summary: This study reveals that the chromatin remodeling complex RSC and general regulatory factors (GRFs) control the directionality of gene promoters by attenuating divergent transcription. RSC affects nucleosome positioning at the sites of divergent transcription, while GRFs suppress divergent transcription initiation.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Kwan Ting Kan, Michael G. Nelson, Chris M. Grant, Simon J. Hubbard, Hui Lu
Summary: Yme1 is a multifunctional protein that plays important roles in maintaining mitochondrial protein homeostasis and regulating biogenesis and function of mitochondrial proteins. This study shows that YME1 deletion affects yeast growth, chronological life span, mitochondrial protein homeostasis and function. It also reveals that Yme1 plays a key role in longevity and is important for maintaining the level and function of mitochondrial oxidative phosphorylation complexes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Sansan Hua, Joana I. Rodrigues, Gabriel Petelski, Lidia A. Esquembre, Emma Lorentzon, Lars F. Olsen, Krzysztof Liberek, Markus J. Tamas, Ursula Jakob, Agnieszka Klosowska
Summary: The toxic metalloid arsenite induces misfolding and aggregation of proteins, which may contribute to the pathology of protein misfolding diseases. This study reveals that the ubiquitin-proteasome system is the main pathway for clearing arsenite-induced protein aggregates, and plays a crucial role in cell growth. The autophagy-vacuole pathway and chaperone-mediated disaggregation also contribute to clearance, but to a lesser extent than the ubiquitin-proteasome system.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biology
Radhika A. Varier, Theodora Sideri, Charlotte Capitanchik, Zornitsa Manova, Enrica Calvani, Alice Rossi, Raghu R. Edupuganti, Imke Ensinck, Vincent W. C. Chan, Harshil Patel, Joanna Kirkpatrick, Peter Faull, Ambrosius P. Snijders, Michiel Vermeulen, Markus Ralser, Jernej Ule, Nicholas M. Luscombe, Folkert J. van Werven
Summary: In this study, we performed a comprehensive analysis of the m6A reader protein Pho92 and found that it promotes protein synthesis and links it to mRNA decay in Saccharomyces cerevisiae. Through its interaction with transcriptional elongator Paf1C, Pho92 associates with target loci and promotes meiosis.
Article
Biochemistry & Molecular Biology
Joana I. Rodrigues, Emma Lorentzon, Sansan Hua, Andrew Boucher, Markus J. Tamas
Summary: Arsenite induces proteotoxicity by causing misfolding and aggregation of nascent proteins. Loss of ribosome-associated chaperones Zuo1, Ssz1, and Ssb1/Ssb2 reduces protein aggregation and increases arsenite resistance. Defective aggregate clearance and arsenite sensitivity are observed with loss of cytosolic GimC/prefoldin function. Ribosome-associated ubiquitin ligases have little contribution to proteostasis during arsenite stress, while cytosolic ubiquitin ligase Rsp5 plays an important role in aggregate clearance and resistance. Our study highlights the importance of damage prevention and elimination mechanisms in maintaining proteostasis during arsenite stress.
Article
Biochemistry & Molecular Biology
Martin D. Jennings, Priya Srivastava, Christopher J. Kershaw, David Talavera, Christopher M. Grant, Graham D. Pavitt
Summary: Cells respond to oxidative stress by reprogramming gene expression to enhance levels of antioxidant enzymes. In Saccharomyces cerevisiae, proteins Slf1 and Sro9 play a role in protein synthesis adaptation during stress. Slf1 is identified as a ribosome-associated translational modulator that promotes translation of highly-translated mRNAs, facilitating cell survival and adaptation to stress.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Imke Ensinck, Theodora Sideri, Miha Modic, Charlotte Capitanchik, Claudia Vivori, Patrick Toolan-Kerr, Folkert J. van Werven
Summary: N6-methyladenosine (m6A) is a widely studied and abundant RNA modification that regulates the fate of RNAs in various ways. To quantify m6A levels, numerous methods have been developed, but they often involve extensive protocols. Here, we present a simple and scalable method, m6A-ELISA, for determining relative m6A levels in mRNA populations from different sources.
Article
Biochemistry & Molecular Biology
Jana Schepers, Zorana Carter, Paraskevi Kritsiligkou, Chris M. Grant
Summary: This study reveals that methionine oxidation is a key factor in the formation of the yeast [PSI+] prion. By lacking methionine sulfoxide reductases, it is found that [PSI+] formation is increased, while lacking both isoenzymes of methionine sulfoxide reductases reduces [PSI+] formation.
Article
Biochemistry & Molecular Biology
Joanne Cunningham, Aristeidis P. Sfakianos, Paraskevi Kritsiligkou, Christopher J. Kershaw, Alan J. Whitmarsh, Simon J. Hubbard, Mark P. Ashe, Chris M. Grant
Summary: Translation initiation factor 4G (eIF4G) is crucial for translation initiation. In yeast, eIF4G1 is specifically required for the translational response to oxidative stress.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Yves Schulze, Payam Ghiaci, Liqian Zhao, Marc Biver, Jonas Warringer, Montserrat Filella, Markus J. Tamas
Summary: Aluminium, gallium, and indium are group 13 metals with similar properties, and their toxic effects and protective mechanisms are poorly understood. This study identifies genes in yeast that play a role in resistance to these metals, providing a basis for further investigations in yeast, plants, and humans.
Article
Biotechnology & Applied Microbiology
Antonia M. Romero, Ewa Maciaszczyk-Dziubinska, Mandana Mombeinipour, Emma Lorentzon, Emelie Aspholm, Robert Wysocki, Markus J. Tamas
Summary: In this study, the researchers found that the protein Etp1 interacts with transcription factors Yap8, Yap1, and Yap6 in yeast. Etp1 was found to be required for optimal growth and expression of the arsenite export protein ACR3 in the presence of arsenic. Interestingly, Etp1 was found to regulate ACR3 expression independently of Yap8. This study provides insights into the gene regulation mechanisms under arsenic and other stress conditions.
FEMS YEAST RESEARCH
(2022)