Article
Biochemistry & Molecular Biology
Siddhi Omkar, Tasaduq H. Wani, Bo Zheng, Megan M. Mitchem, Andrew W. Truman
Summary: This study shows that APE2 and Apn2 proteins depend on the chaperone system in yeast and mammalian cells, and suggests that inhibiting chaperones may be a potential anticancer therapy targeting APE2-mediated processes.
Review
Biochemistry & Molecular Biology
Samarpan Maiti, Didier Picard
Summary: The heat shock protein 90 (Hsp90) is a crucial molecular chaperone and regulator of protein stability in both normal and stressful conditions. In mammals, there are two cytosolic isoforms of Hsp90, Hsp90 alpha and Hsp90 beta, which have overlapping functions and interact with a majority of the proteome. Recent studies suggest that there may be differences in the specific functions of these isoforms, particularly in relation to certain tissues or cell types. Understanding the isoform-specific functions is important for designing therapeutic strategies.
Article
Multidisciplinary Sciences
Benjamin Caballero, Mathieu Bourdenx, Enrique Luengo, Antonio Diaz, Peter Dongmin Sohn, Xu Chen, Chao Wang, Yves R. Juste, Susanne Wegmann, Bindi Patel, Zapporah T. Young, Szu Yu Kuo, Jose Antonio Rodriguez-Navarro, Hao Shao, Manuela G. Lopez, Celeste M. Karch, Alison M. Goate, Jason E. Gestwicki, Bradley T. Hyman, Li Gan, Ana Maria Cuervo
Summary: The study shows that acetylation of tau protein reduces its degradation through chaperone-mediated autophagy, leading to rerouting to other autophagic pathways and increased extracellular release of tau.
NATURE COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Taylor Arhar, Arielle Shkedi, Cory M. Nadel, Jason E. Gestwicki
Summary: Molecular chaperones, despite their diverse sequences, sizes, and shapes, all bind to unfolded proteins to assist in their folding. Recent advancements in NMR spectroscopy have allowed for detailed studies on how different chaperones interact with client proteins. These studies have revealed both similarities and differences in how chaperones release clients and how ATP cycling affects the folding process.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Alexis Tomaszewski, Rebecca Wang, Eduardo Sandoval, Jin Zhu, Jian Liu, Rong Li
Summary: Accumulation of protein aggregates is a hallmark of cellular aging and degenerative disorders. This study reveals that protein aggregates formed under stress can transition from a solid to a liquid state upon stress attenuation, accompanied by a reduction in aggregate number.
Article
Biochemistry & Molecular Biology
Antonio J. Figueira, Guilherme G. Moreira, Joana Saavedra, Isabel Cardoso, Claudio M. Gomes
Summary: The hallmark of Alzheimer's disease (AD) includes the aggregation of amyloid-beta (A beta), tau, and neuroinflammation. In this study, the researchers found that S100B protein, which is upregulated in AD, can inhibit the aggregation of A beta 42, and this activity is dependent on Ca2+ binding. They also discovered that S100B exists in tetrameric form, and tetrameric S100B is more effective in inhibiting A beta 42 aggregation. These findings highlight the importance of S100B protein in regulating AD proteotoxicity.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Chemistry, Analytical
Julius Fuersch, Carsten Voormann, Kai-Michael Kammer, Florian Stengel
Summary: Small heat-shock proteins (sHSPs) play important roles in the cellular stress response across all species, primarily by binding early unfolding states of proteins to prevent aggregation. Research on yeast Hsp26 using cross-linking mass spectrometry (XL-MS) has provided detailed structural information on sHSP activation and client binding, revealing the significance of the middle domain in client-independent interaction and potential client specificity through additional binding sites within its alpha-crystallin domain and C-terminal extension.
ANALYTICAL CHEMISTRY
(2021)
Article
Physics, Multidisciplinary
Lujun Zou, Jiajun Lu, Xiulian Xu
Summary: Protein folding in cells often relies on the assistance of molecular chaperones. In this study, molecular simulations were used to investigate how the interaction strength between the chaperone and client protein modulates the foldase function of Hsp70. The results showed that the folding time of the substrate has a non-monotonic dependence on the interaction strength. When the interaction is too strong, even a small number of contacts can maintain the substrate bound with the chaperone.
Article
Neurosciences
Yuxing Xia, Brach M. M. Bell, Justin D. D. Kim, Benoit I. I. Giasson
Summary: Tauopathies are neurodegenerative diseases characterized by the formation of tau brain aggregates. Imbalance of 3R and 4R tau isoforms is a contributing factor in the development of these diseases. The S356T tau mutation shows unique prion-like seeded aggregation, forming extensive Thioflavin positive aggregates. This finding will contribute to the understanding of diverse presentations of different tauopathies.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Genetics & Heredity
Deepika Gaur, Navinder Kumar, Abhirupa Ghosh, Prashant Singh, Pradeep Kumar, Jyoti Guleria, Satinderdeep Kaur, Nikhil Malik, Sudipto Saha, Thomas Nystrom, Deepak Sharma
Summary: Hsp70 plays a critical role in the Hsp90 chaperoning pathway. Novel mutations in the nucleotide-binding domain of yeast Ssa1 Hsp70 have been identified, which adversely affect Hsp90 client maturation. These mutations result in better binding with Ydj1 and poor growth support in the absence of Sti1. Furthermore, downregulation of pathways involved in signaling, signal transduction, and protein phosphorylation was observed in cells expressing the mutant Hsp70. The study shows that Ydj1 interaction at the nucleotide-binding domain of Ssa1 Hsp70 influences Hsp90 function.
Article
Chemistry, Physical
Erik B. Nordquist, Eugenia M. Clerico, Jianhan Chen, Lila M. Gierasch
Summary: Hsp70 molecular chaperones play vital roles in maintaining cellular proteome. Predicting the binding sites of Hsp70s to their clients provides insights into cellular functions of the chaperone. This article discusses the use of computational modeling and experimental data to understand the selective binding of Hsp70 molecular chaperones to accessible sequences in client proteins.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Biochemical Research Methods
Jennifer Guergues, Jessica Wohlfahrt, Ping Zhang, Bin Liu, Stanley M. Stevens
JOURNAL OF PROTEOMICS
(2020)
Article
Multidisciplinary Sciences
Jennifer N. Rauch, Gabriel Luna, Elmer Guzman, Morgane Audouard, Collin Challis, Youssef E. Sibih, Carolina Leshuk, Israel Hernandez, Susanne Wegmann, Bradley T. Hyman, Viviana Gradinaru, Martin Kampmann, Kenneth S. Kosik
Article
Substance Abuse
Meera Rath, Jennifer Guergues, Joao P. C. Pinho, Ping Zhang, Truc G. Nguyen, Kaley A. MacFadyen, Joanna Peris, Jay P. McLaughlin, Stanley M. Stevens, Bin Liu
ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
(2020)
Article
Cell Biology
Xuemei Zhang, Michael Vigers, James McCarty, Jennifer N. Rauch, Glenn H. Fredrickson, Maxwell Z. Wilson, Joan-Emma Shea, Songi Han, Kenneth S. Kosik
JOURNAL OF CELL BIOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Leah N. Makley, Oleta T. Johnson, Phani Ghanakota, Jennifer N. Rauch, Delaney Osborn, Taia S. Wu, Tomasz Cierpicki, Heather A. Carlson, Jason E. Gestwicki
Summary: Researchers identified potential binding sites in Hsp27 through techniques such as mixed solvent molecular dynamics and NMR solvent mapping, and conducted a fragment-based drug discovery screen. Ultimately, two promising fragments were found, with one fragment significantly increasing affinity under medicinal chemistry intervention while maintaining good ligand efficiency. Additionally, binding to this site partially restored stability of disease-associated Hsp27 variants.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Jennifer N. Rauch, Eric Valois, Sabrina C. Solley, Friederike Braig, Ryan S. Lach, Morgane Audouard, Jose Carlos Ponce-Rojas, Michael S. Costello, Naomi J. Baxter, Kenneth S. Kosik, Carolina Arias, Diego Acosta-Alvear, Maxwell Z. Wilson
Summary: The COVID-19 pandemic has created a massive demand for tools to detect the virus’s genetic material. CREST is a new pipeline that combines common biochemical methods with low-cost instrumentation, providing a solution without sacrificing detection sensitivity.
JOURNAL OF CLINICAL MICROBIOLOGY
(2021)
Article
Biochemical Research Methods
Crystina L. Kriss, Nalvi Duro, Owen W. Nadeau, Jennifer Guergues, Omar Chavez-Chiang, Ashley E. Culver-Cochran, Dale Chaput, Sameer Varma, Stanley M. Stevens
Summary: Oxidative and nitrative stress play a role in various biological processes and diseases, with nitrotyrosine observed in alcohol-induced liver injury. The nitration of histone proteins may induce chromatin structural changes associated with gene transcription processes in alcohol-induced liver injury.
JOURNAL OF MASS SPECTROMETRY
(2021)
Article
Medicine, General & Internal
Jennifer N. Rauch, Eric Valois, Jose Carlos Ponce-Rojas, Zach Aralis, Ryan S. Lach, Francesca Zappa, Morgane Audouard, Sabrina C. Solley, Chinmay Vaidya, Michael Costello, Holly Smith, Ali Javanbakht, Betsy Malear, Laura Polito, Stewart Comer, Katherine Arn, Kenneth S. Kosik, Diego Acosta-Alvear, Maxwell Z. Wilson, Lynn Fitzgibbons, Carolina Arias
Summary: This study investigated the prevalence of SARS-CoV-2 in asymptomatic participants in a university community using a CRISPR-based test. The results showed 8 positive cases among students, highlighting the potential of covert viral transmission and the effectiveness of CRISPR-based assays in capturing positive cases in this population.
Article
Multidisciplinary Sciences
Ravneet Chhabra, Stephanie Rockfield, Jennifer Guergues, Owen W. Nadeau, Robert Hill, Stanley M. Stevens, Meera Nanjundan
Summary: Malignant transformation of fallopian tube secretory epithelial cells (FTSECs) induced by chronic iron exposure involves increased expression of oncogenic mediators, telomerase transcripts, and growth/migratory potential. Global miRNA and protein alterations in iron-exposed FTSECs may be regulated by genome-wide epigenetic changes, potentially serving as future biomarkers for early ovarian cancer detection and therapeutic targets.
SCIENTIFIC REPORTS
(2021)
Article
Substance Abuse
Meera Rath, Jasmin Tawfic, Aziza Abrorkhujaeva, Sam Sowell, Sara Wu, Shainnel O. Eans, Joanna Peris, Jay P. McLaughlin, Stanley M. Stevens, Bin Liu
Summary: The study successfully modeled acute movement impairments and anxiety-like behaviors in mice after binge ethanol consumption using a modified drinking-in-the-dark model. The individual mice's ethanol intake positively correlated with blood ethanol concentration levels.
Article
Biochemistry & Molecular Biology
Ahmad Jalloh, Antwoine Flowers, Charles Hudson, Dale Chaput, Jennifer Guergues, Stanley M. Stevens, Paula C. Bickford
Summary: Research indicates that microglial activity is a central factor in aging-related dysfunction, with protein signaling cascades playing a key role in altering microglial function. Polyphenols may offer a means of addressing age-related decline, highlighting their potential therapeutic role in age-associated dysfunction.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Santiago Rodriguez Ospina, Danielle M. Blazier, Marangelie Criado-Marrero, Lauren A. Gould, Niat T. Gebru, David Beaulieu-Abdelahad, Xinming Wang, Elizabeth Remily-Wood, Dale Chaput, Stanley Stevens, Vladimir N. Uversky, Paula C. Bickford, Chad A. Dickey, Laura J. Blair
Summary: The study found that overexpression of Hsp22 can protect synaptic plasticity and cognition in tauopathic brains, without significantly altering tau phosphorylation levels. Mass spectrometry analysis revealed that Hsp22 overexpression in neurons promotes synaptic plasticity by regulating canonical pathways and upstream regulators related to potential AD markers and synaptogenesis regulators.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemical Research Methods
Ping Zhang, Jennifer Guergues, Amy R. Alleyne, Thomas J. Cirino, Owen Nadeau, Ariana M. Figueroa, Heather M. Stacy, Takayoshi Suzuki, Jay P. McLaughlin, Stanley M. Stevens, Bin Liu
Summary: This study identified specific histone protein modifications associated with chronic pain in microglia, providing critical insight into the contribution of microglia to pain development and maintenance. The findings suggest that targeting these chromatin marks may lead to the development of novel nonopioid therapeutics for chronic pain management.
Article
Biochemical Research Methods
Jennifer Guergues, Jessica Wohlfahrt, Stanley M. Stevens
Summary: This study used TIMS to fractionate ions in the gas phase and combined it with PASEF for protein and peptide analysis. The results showed that TIMS fractionation significantly increased the number of protein and peptide identifications without affecting quantitation precision.
JOURNAL OF PROTEOME RESEARCH
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jennifer Rauch