Article
Biochemistry & Molecular Biology
Lydia K. Muranova, Vladislav M. Shatov, Andrei V. Slushchev, Nikolai B. Gusev
Summary: It is suggested that small heat shock proteins interact directly with actin and have an impact on the formation and stability of actin filaments. However, the analysis of the interaction between recombinant human small heat shock protein HspB7 and skeletal muscle actin revealed that HspB7 is not a genuine actin-binding protein. Its effect on actin filaments seems to be determined by its interaction with minor regulatory proteins of actin filaments.
Article
Biochemistry & Molecular Biology
V. Sudhakar Reddy, S. Pandarinath, M. Archana, G. Bhanuprakash Reddy
Summary: Chronic hyperglycemia induces differential responses of sHsps by altering their expression, solubility, interaction, and roles in apoptosis in neuronal cells, potentially contributing to cell death.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
Review
Biochemistry & Molecular Biology
Bianca Nitzsche, Michael Hoepfner, Bernhard Biersack
Summary: Heat shock protein 70 (Hsp70) and its interaction with Hsp90 play a significant role in cancer diseases. The Hsp70-Hsp40 axis, formed by the connection between Hsp70 and a smaller heat shock protein Hsp40, is a suitable target for designing anticancer drugs. This review discusses the current state and recent developments in the field of (semi-)synthetic small molecule inhibitors targeting Hsp70 and Hsp40, as well as their potential in medicinal chemistry and anticancer therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Lydia K. Muranova, Vladislav M. Shatov, Andrey Slushchev, Nikolai B. Gusev
Summary: In this study, a reliable and simple method to prepare untagged recombinant human HspB7 was developed. It was found that HspB7 can form different oligomeric structures under different conditions, and the factors influencing the formation of these oligomers were investigated.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Plant Sciences
Baptiste Bourgine, Anthony Guihur
Summary: Heat stress events limit crop productivity, leading plants to accumulate heat-shock proteins (HSPs) for thermal protection. HSP chaperones play a critical role in regulating protein folding and preventing misfolded protein formation, thereby avoiding heat-induced cell death. The HSP20 family is tightly repressed at low temperatures, suggesting a costly mechanism that can become detrimental under unnecessary conditions.
FRONTIERS IN PLANT SCIENCE
(2021)
Article
Cell & Tissue Engineering
Ju-Fang Liu, Po-Chun Chen, Thai-Yen Ling, Chun-Han Hou
Summary: This study demonstrates that heat shock induces the expression of HSPs in hPDMCs through the activation of ROS, p38 MAPK, Akt signaling, and HSF1, which plays a protective role.
STEM CELL RESEARCH & THERAPY
(2022)
Review
Cell Biology
Ariadni Androvitsanea, Kostas Stylianou, Eleni Drosataki, Ioannis Petrakis
Summary: Research has shown that heat-shock proteins can have varying effects on the immune system, either triggering immune responses or alleviating them, which is important for studying and treating autoimmune diseases.
Article
Chemistry, Multidisciplinary
Aaron T. Balana, Paul M. Levine, Timothy W. Craven, Somnath Mukherjee, Nichole J. Pedowitz, Stuart P. Moon, Terry T. Takahashi, Christian F. W. Becker, David Baker, Matthew R. Pratt
Summary: The study found that O-GlcNAc can activate the anti-amyloid activity of certain small heat shock proteins, inhibiting protein aggregation. Although O-GlcNAc levels are globally reduced in Alzheimer's disease brains, the modification of relevant small heat shock proteins is either maintained or increased, suggesting a mechanism to maintain these potentially protective O-GlcNAc modifications.
Article
Oncology
Ting Song, Yafei Guo, Zuguang Xue, Zongwei Guo, Ziqian Wang, Donghai Lin, Hong Zhang, Hao Pan, Xiaodong Zhang, Fangkui Yin, Hang Wang, Laura Bonnette Uwituze, Zhichao Zhang
Summary: S1g-2, a novel inhibitor targeting Hsp70-Bim PPI, exhibits higher apoptosis-inducing activity in CML and disrupts BCR-ABL-driven interaction, showing potential therapeutic value in both TKI-sensitive and resistant CML patients.
Article
Biochemistry & Molecular Biology
Binyou Wang, Stuart P. Moon, Giuliano Cutolo, Afraah Javed, Benjamin S. Ahn, Andrew H. Ryu, Matthew R. Pratt
Summary: O-GlcNAc modification protects cells against stress-induced cell death by directly inhibiting the apoptotic pathway. The modified chaperone, HSP27, exhibits enhanced antiapoptotic function in an in vitro context. These findings provide molecular insights into how O-GlcNAc serves as a mediator of cellular stress and have important implications for human diseases like cancer and neurodegeneration.
ACS CHEMICAL BIOLOGY
(2023)
Article
Plant Sciences
Anthony Guihur, Bruno Fauvet, Andrija Finka, Manfredo Quadroni, Pierre Goloubinoff
Summary: In the scorching summer dawn, land plants establish molecular defenses to prepare for extreme midday temperatures, inducing heat-shock proteins for acquired thermotolerance. Despite high protein crowding, heat priming did not accumulate HSP chaperones in chloroplasts, while HSP20s accumulated in the cytosol, suggesting their role in preventing heat-labile protein aggregation.
PLANT CELL AND ENVIRONMENT
(2021)
Article
Multidisciplinary Sciences
Ahmed Barakat, Even Birkeland, Melissa D. Jorstad, Magalie El Hajj, Msafiri Marijani, Anne Doskeland, Olav Mjaavatten, Frode S. Berven, Tehmina Mustafa
Summary: This study investigated the proteomic profile of PBMCs in pulmonary tuberculosis (PTB) patients to predict treatment response. Blood samples were collected from 8 adult PTB patients in Tanzania at baseline, 2 months of treatment, and treatment completion. Proteins extracted from PBMCs were quantified and analyzed using LC-MS/MS. The results identified differentially expressed proteins involved in cellular processes, metabolic processes, binding, and catalytic activity, suggesting that proteome analysis of PBMCs can be used as a novel technique to monitor anti-tuberculosis treatment response and gain insights into PTB.
Article
Plant Sciences
Tung-Yi Lin, Wei-Jyun Hua, Hsin Yeh, Ai-Jung Tseng
Summary: The study demonstrates that FIPs LZ-8 and GMI induce changes in the proteomic profile of tumor lesions in LLC1 cell-bearing mouse, potentially regulating heat shock proteins (HSPs)-related cell viability and inhibiting cell migration and inducing apoptosis. Inhibition of HSPs may contribute to the anti-lung cancer activity of FIPs.
Article
Biochemistry & Molecular Biology
Mehdi Basaki, Kamran Keykavusi, Nazila Sahraiy, Ghasem Akbari, Marzieh Hejazi
Summary: This study investigated the effects of iron oxide nanoparticles on the mRNA expression of small heat shock proteins in chicken embryos, revealing differential expression patterns and suggesting a protective cellular mechanism against nanoparticles through these proteins.
BIOLOGICAL TRACE ELEMENT RESEARCH
(2022)
Article
Agriculture, Dairy & Animal Science
Roland Toth, Nikolett Tokodyne Szabadi, Bence Lazar, Kitti Buda, Barbara Vegi, Judit Barna, Eszter Patakine Varkonyi, Krisztina Liptoi, Bertrand Pain, Elen Gocza
Summary: Heat stress from high environmental temperatures can negatively affect animal productivity, with studies showing a significant increase in the expression levels of HSP90 and HSF4 in heat-treated female chicken gonads.
Article
Biochemistry & Molecular Biology
Adam Kanack, Vinayak Vittal, Holly Haver, Theodore Keppel, Rebekah L. Gundry, Rachel E. Klevit, Kenneth Matthew Scaglione
Article
Multidisciplinary Sciences
Kedar Puvar, Shalini Iyer, Jiaqi Fu, Sebastian Kenny, Kristos I. Negron Teron, Zhao-Qing Luo, Peter S. Brzovic, Rachel E. Klevit, Chittaranjan Das
NATURE COMMUNICATIONS
(2020)
Article
Biochemistry & Molecular Biology
Christian Lips, Tobias Ritterhoff, Annika Weber, Maria K. Janowska, Mandy Mustroph, Thomas Sommer, Rachel E. Klevit
Article
Biochemistry & Molecular Biology
Samuel R. Witus, Anika L. Burrell, Daniel P. Farrell, Jianming Kang, Meiling Wang, Jesse M. Hansen, Alex Pravat, Lisa M. Tuttle, Mikaela D. Stewart, Peter S. Brzovic, Champak Chatterjee, Weixing Zhao, Frank DiMaio, Justin M. Kollman, Rachel E. Klevit
Summary: Mutations in the RING domains of the E3 ubiquitin ligase BRCA1/BARD1 increase the risk of breast and ovarian cancers. The structure of the BRCA1/BARD1 RING heterodimer with UbcH5c bound to the nucleosome, along with biochemical data, explains how the complex selectively ubiquitylates specific lysines in H2A. The findings provide insight into how E3 ligases target lysine residues in nucleosomes and how mutations in cancer patients affect this process.
NATURE STRUCTURAL & MOLECULAR BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Lisa M. Tuttle, Derek Pacheco, Linda Warfield, Damien B. Wilburn, Steven Hahn, Rachel E. Klevit
Summary: The acidic activation domain (AD) of the yeast transcription factor Gal4 acts through binding to the Med15 subunit of the Mediator complex. The interaction between Gal4 and Med15 occurs through the same fuzzy binding mechanism as Gcn4 AD, indicating a common sequence-independent mechanism for AD-Mediator binding. Conversely, the structured binding partner Gal80 determines the type of protein-protein interaction for the intrinsically disordered protein Gal4 AD.
NATURE COMMUNICATIONS
(2021)
Article
Microbiology
Dagmara Kisiela, Pearl Magala, Gianluca Interlandi, Laura A. Carlucci, Angelo Ramos, Veronika Tchesnokova, Benjamin Basanta, Vladimir Yarov-Yarovoy, Hovhannes Avagyan, Anahit Hovhannisyan, Wendy E. Thomas, Ronald E. Stenkamp, Rachel E. Klevit, Evgeni Sokurenko
Summary: The study identified a novel antibody that acts as a kinetic trap to prevent the conformational transitions of FimH protein, leading to a significant slowing down of its ability to bind mannose and blocking bacterial adhesion. Residues Leu-34 and Val-35 of FimH were found to act as molecular toggle switches, which, when disrupted, hinder the conformational transition and adhesive function of the protein. The research also demonstrated that the allosteric switches are conserved across a diverse family of bacterial fimbrial adhesins.
Biographical-Item
Multidisciplinary Sciences
John D. Scott, Trisha N. Davis, Rachel E. Klevit, William A. Catterall
Review
Biochemistry & Molecular Biology
Samuel R. Witus, Weixing Zhao, Peter S. Brzovic, Rachel E. Klevit
Summary: Mutations in BRCA1 and BARD1 predispose carriers to breast and ovarian cancers. Recent advancements in structural and cellular biology have provided critical insights into how BRCA1/BARD1 serves as a nucleosome reader and writer, facilitating transcriptional regulation and DNA repair.
TRENDS IN BIOCHEMICAL SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Evgeni Sokurenko, Veronika Tchesnokova, Gianluca Interlandi, Rachel Klevit, Wendy E. Thomas
Summary: This article summarizes studies on various functional types of monoclonal antibodies obtained against different allosteric conformers of the mannose-specific bacterial adhesin FimH. Understanding the molecular mechanism of antibody action against allosteric proteins provides insights on how to design antibodies with desired functional effects, including those with neutralizing activity against bacterial and viral cell attachment proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Katherine H. Reiter, Alex Zelter, Maria K. Janowska, Michael Riffle, Nicholas Shulman, Brendan X. MacLean, Kaipo Tamura, Matthew C. Chambers, Michael J. MacCoss, Trisha N. Davis, Miklos Guttman, Peter S. Brzovic, Rachel E. Klevit
Summary: This study characterized the interaction between the auto-inhibited RBR ligase HHARI and its substrate 4EHP using a combination of techniques. The results revealed a binding platform on the catalytic domain of HHARI and the role of a phosphomimetic mutation in promoting the release and reorientation of Rcat for substrate modification. These findings identify a direct binding interaction between an RBR ligase and its substrate and propose a general model for substrate recognition.
Article
Biology
Eugene Serebryany, Sourav Chowdhury, Christopher N. Woods, David C. Thorn, Nicki E. Watson, Arthur A. McClelland, Rachel E. Klevit, Eugene Shakhnovich
Summary: Cataract, a protein aggregation disorder, is a common cause of vision loss worldwide. Researchers have discovered that myo-inositol, an abundant lens metabolite, can suppress the aggregation of lens crystallins, suggesting it as a potential strategy to prevent or delay age-onset cataracts.
Article
Biochemistry & Molecular Biology
Ishor Thapa, Russell Vahrenkamp, Samuel R. Witus, Caitlin Lightle, Owen Falkenberg, Marlo K. Sellin Jeffries, Rachel E. Klevit, Mikaela D. Stewart
Summary: The tumor-suppressor proteins BRCA1 and BARD1 play important roles in transcriptional repression and DNA damage repair, and their functions are mediated through mono-ubiquitylation of histone H2A in nucleosomes. The study in C. elegans reveals that the orthologs BRC-1 and BRD-1 retain many functions of their human counterparts, including enzymatic activity toward nucleosomes. Despite differences in binding modes, BRC-1 and BRD-1 also contribute to gene repression in C. elegans. This highlights the conservation of these functions and allows further investigation using this model organism.
NUCLEIC ACIDS RESEARCH
(2023)
Meeting Abstract
Biophysics
Rachel Klevit, Amanda F. Clouser, Hannah E. E. R. Baughman, Chris Woods, Maria Janowska, Natalie Stone, Lindsey Ulmer, Matt Bush, Miklos Guttman
BIOPHYSICAL JOURNAL
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Russell Vahrenkamp, Sam Witus, Rachel Klevit, Mikaela Stewart