We report the application of pressure perturbation calorimetry (PPC) to study unfolded proteins. Using PPC we have measured the temperature dependence of the thermal expansion coefficient, α(T), in the unfolded state of apocytochrome C and reduced BPTI. We have shown that α(T) is a nonlinear function and decreases with increasing temperature. The decrease is most significant in the low (2-55 °C) temperature range. We have also tested an empirical additivity approach to predict α(T) of unfolded state from the amino acid sequence using α(T) values for individual amino acids. A comparison of the experimental and calculated functions shows a very good agreement, both in absolute values of α(T) and in its temperature dependence. Such an agreement suggests the applicability of using empirical calculations to predict α(T) of any unfolded protein.
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http://dx.doi.org/10.1021/jp106294p | DOI Listing |
PLoS One
September 2024
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Florida, Gainesville, Florida, United States of America.
Background: Alpha-1 antitrypsin deficiency (AATD) is an inherited disease, the common variant caused by a Pi*Z mutation in the SERPINA1 gene. Pi*Z AAT increases the risk of pulmonary emphysema and liver disease. Berberine (BBR) is a nature dietary supplement and herbal remedy.
View Article and Find Full Text PDFBiochim Biophys Acta Gene Regul Mech
September 2023
Division of Geriatrics, Gerontology, and Palliative Medicine, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, United States of America. Electronic address:
The loss of proteostasis due to reduced efficiency of protein degradation pathways plays a key role in multiple age-related diseases and is a hallmark of the aging process. Paradoxically, we have previously reported that the Caenorhabditis elegans rpn-10(ok1865) mutant, which lacks the RPN-10/RPN10/PSMD4 subunit of the 19S regulatory particle of the 26S proteasome, exhibits enhanced cytosolic proteostasis, elevated stress resistance and extended lifespan, despite possessing reduced proteasome function. However, the response of this mutant against threats to endoplasmic reticulum (ER) homeostasis and proteostasis was unknown.
View Article and Find Full Text PDFCell Chem Biol
January 2023
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, USA. Electronic address:
Genetic variation in alpha-1 antitrypsin (AAT) causes AAT deficiency (AATD) through liver aggregation-associated gain-of-toxic pathology and/or insufficient AAT activity in the lung manifesting as chronic obstructive pulmonary disease (COPD). Here, we utilize 71 AATD-associated variants as input through Gaussian process (GP)-based machine learning to study the correction of AAT folding and function at a residue-by-residue level by pharmacological activation of the ATF6 arm of the unfolded protein response (UPR). We show that ATF6 activators increase AAT neutrophil elastase (NE) inhibitory activity, while reducing polymer accumulation for the majority of AATD variants, including the prominent Z variant.
View Article and Find Full Text PDFInt J Biol Macromol
February 2023
Amity Institute of Biotechnology, Amity University Uttar Pradesh, Sector 125, Noida 201303, UP, India. Electronic address:
Cymbopogon is an important aromatic and medicinal grass with several species of ethnopharmaceutical importance. The genus is extremely rich in secondary metabolites, monoterpenes like geraniol and citral being principal constituents, also used as biomarker for classification and identification of Cymbopogon chemotypes. In the light of this, present study involved RNA sequencing and comparison of expression profiles of four contrasting Cymbopogon species namely C.
View Article and Find Full Text PDFCell Rep
December 2022
Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address:
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