Article
Biochemistry & Molecular Biology
Huafeng Xu
Summary: Recent experimental studies have shown that ATP-driven molecular chaperones can stabilize protein substrates in their native structures out of thermal equilibrium. This article proposes a unifying principle based on available evidence, which explains the conversion of chemical energy from ATP hydrolysis to the conformational free energy associated with protein folding and activation.
Article
Cell Biology
I-Hui Wu, Jae Seok Yoon, Qian Yang, Yi Liu, William Skach, Philip Thomas
Summary: The study reveals an essential role of mammalian RAC in the unfolded protein response (UPR) and its involvement in modulating IRE1 branch activation. RAC is shown to regulate the clustering of IRE1 alpha, which is crucial for endonuclease activation and splicing of Xbp1 mRNA substrate.
Review
Biochemistry & Molecular Biology
Barbara Tedesco, Veronica Ferrari, Marta Cozzi, Marta Chierichetti, Elena Casarotto, Paola Pramaggiore, Francesco Mina, Mariarita Galbiati, Paola Rusmini, Valeria Crippa, Riccardo Cristofani, Angelo Poletti
Summary: Motoneuron diseases (MNDs) are neurodegenerative conditions associated with death of upper and/or lower motoneurons (MNs). Protein misfolding and defects in the protein quality control system are key factors in MND pathogenesis. Heat Shock Protein 70 (HSP70) and small heat shock proteins (sHSPs/HSPBs) play important roles in maintaining proteostasis and protecting against proteotoxicity in MNDs. Understanding the role of HSPBs in MNDs may provide insights for developing therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Oncology
Gintvile Valinciute, Martine F. Roussel
Summary: Selective targeting of N-Myc-driven Sonic hedgehog (SHH) medulloblastoma has been a long-standing challenge, with limited targeted therapy opportunities. A recent study by Kuzuoglu-Ozturk et al. characterized the translatome of N-Myc-driven medulloblastoma and identified potential therapeutic targets. The study demonstrated that the protein folding machinery controlled by N-Myc could be pharmacologically inhibited, and validated the necessity of certain Hsp70 functions for medulloblastoma progression in vitro and in vivo.
MOLECULAR ONCOLOGY
(2023)
Review
Cell Biology
Kobi Simpson-Lavy, Martin Kupiec
Summary: Cellular processes rely on buffering mechanisms to stabilize against noise, such as in the cell cycle and metabolic regulation. Recent research has highlighted the importance of protein aggregation/condensation as a regulatory mechanism. This article explores the regulation of Std1 and metabolic signaling and enzymatic protein foci through chaperones, anti-aggregases, and phosphorylation.
CURRENT OPINION IN CELL BIOLOGY
(2021)
Article
Pharmacology & Pharmacy
Magdalena Zabinska, Lidia Gaffke, Patrycja Bielanska, Magdalena Podlacha, Estera Rintz, Zuzanna Cyske, Grzegorz Wegrzyn, Karolina Pierzynowska
Summary: Mucopolysaccharidoses (MPS) are rare genetic disorders characterized by the accumulation of glycosaminoglycans (GAGs) in lysosomes due to mutations in lysosomal enzymes. This study found significantly reduced levels of chaperone proteins Hsp70 and Hsp40 in MPS cells. Lowering GAG levels did not normalize chaperone levels, suggesting that reduced chaperone levels may contribute to the low activity of lysosomal enzymes in MPS.
Article
Multidisciplinary Sciences
Yan Chen, Bin Tsai, Ningning Li, Ning Gao
Summary: The authors report structures of RAC-containing ribosomal complexes, providing insights into the dynamic actions of RAC-Ssb during co-translational folding.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Viraj P. Ichhaporia, Linda M. Hendershot
Summary: Cell surface and secreted proteins are essential for multicellular life and undergo maturation and folding in the endoplasmic reticulum (ER). BiP, an ER chaperone, plays a key role in assisting unfolded client proteins. Loss of SIL1 function is a leading cause of Marinesco-Sjogren syndrome (MSS). Understanding the molecular mechanisms of SIL1's NEF activity may lead to new pharmacological approaches for treating MSS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biophysics
Jiajun Lu, Xiaoyi Zhang, Yichao Wu, Yuebiao Sheng, Wenfei Li, Wei Wang
Summary: Through molecular simulations, it was discovered that Hsp70 maintains contact with substrate proteins during the folding process, shielding vulnerable sites to prevent misfolding and increasing folding efficiency. This suggests that in addition to its previously known functions, Hsp70 can facilitate folding by remodeling the energy landscape and directing the folding process, demonstrating a foldase scenario. These findings provide new insights into the molecular mechanisms of chaperone-mediated protein folding.
BIOPHYSICAL JOURNAL
(2021)
Review
Biochemistry & Molecular Biology
Allison A. Dilliott, Catherine M. Andary, Meaghan Stoltz, Andrey A. Petropavlovskiy, Sali M. K. Farhan, Martin L. Duennwald
Summary: Protein misfolding is a common basis for neurodegenerative diseases like ALS. Cellular protein quality control can prevent misfolding, but stressors like reactive oxygen species, genetic mutations, and aging can lead to misfolding. DnaJC7, a molecular chaperone, can prevent misfolding and deal with misfolded proteins through degradation systems or autophagy. Pathogenic variants in the DnaJC7 gene contribute to ALS, but the underlying molecular pathophysiology and function of DnaJC7 remain largely unknown.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Ying Wang, Hongtao Li, Cancan Sun, Qingdai Liu, Lei Zhou, Qinglian Liu
Summary: Hsp110s play important roles in maintaining cellular protein homeostasis, with Msi3 being the only Hsp110 in Candida albicans essential for its growth and infection. Msi3 shares many biochemical activities with the well-characterized Hsp110 Sse1, making it a potential model for studying Hsp110s.
CELL STRESS & CHAPERONES
(2021)
Article
Biochemistry & Molecular Biology
Yoshiko Nakagawa, Howard C-H Shen, Yusuke Komi, Shinju Sugiyama, Takaaki Kurinomaru, Yuri Tomabechi, Elena Krayukhina, Kenji Okamoto, Takeshi Yokoyama, Mikako Shirouzu, Susumu Uchiyama, Megumi Inaba, Tatsuya Niwa, Yasushi Sako, Hideki Taguchi, Motomasa Tanaka
Summary: This study established a robust in vitro reconstituted system of yeast prion propagation and found that Hsp104, Ssa1, and Sis1 chaperones are essential for efficient disaggregation of Sup35 amyloid. They also uncovered two distinct prion strain conformation-dependent modes of disaggregation, fragmentation, and dissolution.
NATURE CHEMICAL BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yassin Ben-Khoud, Chao-Sheng Chen, Maruf M. U. Ali
Summary: Hsp70 molecular chaperones are vital for maintaining protein homeostasis. They interact with client proteins in a regulated manner, supported by ATP and co-chaperones. Recent findings suggest a novel type of interaction between Hsp70 and client proteins, termed Hsp70 ATPase alternative binding proteins or HAAB proteins. Common mechanistic features of Hsp70 in this alternative mode of action are identified.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2023)
Article
Multidisciplinary Sciences
Nicholas R. Marzano, Bishnu P. Paudel, Antoine M. van Oijen, Heath Ecroyd
Summary: The study used total internal reflection fluorescence (TIRF) microscopy and single-molecule fluorescence resonance energy transfer (smFRET) to observe the folding process of firefly luciferase proteins mediated by the bacterial Hsp70 system. The researchers found that there are multiple cycles of chaperone binding and release to individual clients during refolding, and high rates of chaperone cycling improve refolding yield. Additionally, they discovered that DnaJ remodels misfolded proteins through a conformational selection mechanism, while DnaK resolves misfolded states through mechanical unfolding. This study elucidates important mechanistic details of chaperone-assisted folding that are inaccessible using other methods.
Article
Pediatrics
Pinja Tissarinen, Heli Tiensuu, Antti M. M. Haapalainen, Tomi A. A. Maatta, Marja Ojaniemi, Mikko Hallman, Mika Ramet
Summary: This study investigated the localization and roles of heat shock protein HSPA5 in spontaneous preterm birth (SPTB). The results showed that HSPA5 was upregulated in placentas from SPTB. Silencing of HSPA5 in human trophoblast cells promoted the inflammatory response and decreased the expression of proinflammatory genes.
PEDIATRIC RESEARCH
(2023)
Article
Microbiology
Balint Kintses, Orsolya Mehi, Eszter Ari, Monika Szamel, Adam Gyorkei, Pramod K. Jangir, Istvan Nagy, Ferenc Pal, Gergely Fekete, Roland Tengolics, Akos Nyerges, Istvan Liko, Anita Balint, Tamas Molnar, Balazs Balint, Balint Mark Vasarhelyi, Misshelle Bustamante, Balazs Papp, Csaba Pal
NATURE MICROBIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Zsolt Merenyi, Arun N. Prasanna, Zheng Wang, Karoly Kovacs, Botond Hegedus, Balazs Balint, Balazs Papp, Jeffrey P. Townsend, Laszlo G. Nagy
MOLECULAR BIOLOGY AND EVOLUTION
(2020)
Article
Multidisciplinary Sciences
Viktor Vernyik, Ildiko Karcagi, Edit Timar, Istvan Nagy, Adam Gyoerkei, Balazs Papp, Zsuzsanna Gyoerfy, Gyoergy Posfai
SCIENTIFIC REPORTS
(2020)
Article
Biochemistry & Molecular Biology
Reka Hollandi, Abel Szkalisity, Timea Toth, Ervin Tasnadi, Csaba Molnar, Botond Mathe, Istvan Grexa, Jozsef Molnar, Arpad Balind, Mate Gorbe, Maria Kovacs, Ede Migh, Allen Goodman, Tamas Balassa, Krisztian Koos, Wenyu Wang, Juan Carlos Caicedo, Norbert Bara, Ferenc Kovacs, Lassi Paavolainen, Tivadar Danka, Andras Kriston, Anne Elizabeth Carpenter, Kevin Smith, Peter Horvath
Review
Biochemistry & Molecular Biology
Andrea Ronavari, Nora Igaz, Dora I. Adamecz, Bettina Szerencses, Csaba Molnar, Zoltan Konya, Ilona Pfeiffer, Monika Kiricsi
Summary: The nanomaterial industry produces large quantities of metal-based nanomaterials for various applications, but the use of toxic chemicals for production burdens the environment. Green synthetic approaches have emerged to provide eco-friendly alternative methods and reduce the ecological footprint.
Correction
Biochemistry & Molecular Biology
Gabor Apjok, Gabor Boross, Akos Nyerges, Gergely Fekete, Viktoria Lazar, Balazs Papp, Csaba Pal, Balint Csoergo
MOLECULAR BIOLOGY AND EVOLUTION
(2021)
Article
Multidisciplinary Sciences
Abel Szkalisity, Filippo Piccinini, Attila Beleon, Tamas Balassa, Istvan Gergely Varga, Ede Migh, Csaba Molnar, Lassi Paavolainen, Sanna Timonen, Indranil Banerjee, Elina Ikonen, Yohei Yamauchi, Istvan Ando, Jaakko Peltonen, Vilja Pietiainen, Viktor Honti, Peter Horvath
Summary: The use of Regression Plane as a user-friendly discovery tool enables continuous phenotypic supervised machine learning in biological data exploration. The approach has the potential for application in experimental data processing and novel discoveries.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Alexandra Imre, Renato Kovacs, Kitti Pazmandi, Daniel Nemes, Agnes Jakab, Tunde Fekete, Hanna Viktoria Racz, Ilona Doczi, Ildiko Bacskay, Attila Gacser, Karoly Kovacs, Laszlo Majoros, Zoltan Farkas, Istvan Pocsi, Walter P. Pfliegler
Summary: Research has found that Saccharomyces yeast probiotics may possess potential pathogenic characteristics and display new traits as they evolve within the host. While there are some differences, the yeast does not show significant pathogenicity in the host and its entry into the bloodstream is not active. These findings highlight the need for a more thorough assessment of probiotic use.
Article
Biochemistry & Molecular Biology
Mattia Pavani, Paolo Bonaiuti, Elena Chiroli, Fridolin Gross, Federica Natali, Francesca Macaluso, Adam Poti, Sebastiano Pasqualato, Zoltan Farkas, Simone Pompei, Marco Cosentino Lagomarsino, Giulia Rancati, David Szuts, Andrea Ciliberto
Summary: Cells with blocked microtubule polymerization can eventually proliferate despite chromosome missegregation, and through laboratory evolution, they can regain the ability to form microtubules and become less sensitive to microtubule-depolymerizing drugs. The study identified recurrently mutated genes, particularly for tubulins and kinesins, as well as duplication of chromosome VIII, which allowed cells to compensate for the original mutation. Analysis revealed a consistent series of events in the development of resistance, indicating the importance of chromosome duplication followed by adaptive mutations in tubulins or kinesins.
Article
Oncology
Maryam Yousefi, Gabor Boross, Carly Weiss, Christopher W. Murray, Jess D. Hebert, Hongchen Cai, Emily L. Ashkin, Saswati Karmakar, Laura Andrejka, Leo Chen, Minwei Wang, Min K. Tsai, Wen-Yang Lin, Chuan Li, Pegah Yakhchalian, Caterina Colon, Su-Kit Chew, Pauline Chu, Charles Swanton, Christian A. Kunder, Dmitri A. Petrov, Monte M. Winslow
Summary: This study reveals the driver pathways of oncogene-negative lung adenocarcinomas and demonstrates their therapeutic vulnerabilities.
Article
Ecology
Zoltan Farkas, Karoly Kovacs, Zsuzsa Sarkadi, Dorottya Kalapis, Gergely Fekete, Fanni Birtyik, Ferhan Ayaydin, Csaba Molnar, Peter Horvath, Csaba Pal, Balazs Papp
Summary: This study demonstrates that compensatory evolution following gene loss plays a significant role in the rapid emergence of new cellular and multicellular morphologies. Unexpectedly, invasive growth, multicellular aggregation, and biofilm formation also evolve spontaneously in response to gene loss. These traits originate as pleiotropic side effects of compensatory evolution and have ecologically and clinically relevant implications.
NATURE ECOLOGY & EVOLUTION
(2022)
Article
Multidisciplinary Sciences
Judit Amon, Gabriella Varga, Ilona Pfeiffer, Zoltan Farkas, Zoltan Karacsony, Zsofia Hegedus, Csaba Vagvolgyi, Zsuzsanna Hamari
Summary: In this study, the function of HmbA, the Aspergillus nidulans orthologue of Nhp6p, was investigated. It was found that HmbA plays important roles in various physiological processes, such as carbon and nitrogen source utilization, stress tolerance, secondary metabolism, hyphae elongation, and maintenance of polarized growth. The study also demonstrated partial interchangeability between HmbA and Nhp6p.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Orsolya Liska, Gabor Borossb, Charles Rocabert, Balazs Szappanosa, Roland Tengolics, Balazs Papp
Summary: This study introduces a measure of conservation of individual metabolite levels among related species and reveals the association between conservation and functional properties of metabolites. It shows that metabolite abundance, essentiality, and association with human diseases predict conservation, suggesting a parallel between metabolome and protein sequence conservation. Additionally, the study demonstrates that biomarkers of metabolic diseases can be distinguished based on evolutionary conservation alone, without prior clinical knowledge.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Karoly Kovacs, Zoltan Farkas, Djordje Bajic, Dorottya Kalapis, Andreea Daraba, Karola Almasi, Balint Kintses, Zoltan Bodi, Richard A. Notebaart, Juan F. Poyatos, Patrick Kemmeren, Frank C. P. Holstege, Csaba Pal, Balazs Papp
Summary: The rewiring of the transcriptome upon gene inactivation is often nonspecific and mimics stereotypic responses to external environmental changes. Most transcriptomic changes after gene deletion are not specific to the deleted gene, but rather triggered by perturbations in functionally diverse genes. Additionally, gene deletions that alter the expression of dosage-sensitive genes can be particularly harmful.
MOLECULAR BIOLOGY AND EVOLUTION
(2021)