Despite continuing interest in partly unfolded proteins as precursors for aggregation and adverse gain-of-function in human disease, there is yet little known about the local transitions of native structures that possibly lead to such intermediate states. To target this problem, we present here a protein-design strategy that allows real-time detection of rupture and swapping of complete secondary-structure elements in globular proteins-molecular events that have previously been inaccessible experimental analysis. The approach is applied to the dynamic β-barrel of SOD1, associated with pathologic aggregation in the neurodegenerative disease ALS. Data show that rupture and re-insertion of individual β-strands do not take place locally but require the SOD1 barrel to unfold globally. The finding questions the very existence of partly unfolded intermediates in the SOD1 aggregation process and presents new clues to the mechanism by which hydrogen bonding maintains global structural integrity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1021/jacs.6b05151 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Characterization of UGT8 as a monogalactosyl diacylglycerol synthase in mammals.
J Biochem
December 2024
Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Minato-ku, Tokyo 105-8512, Japan.
Monogalactosyl diacylglycerol (MGDG) is a major membrane lipid component in plants and is crucial for proper thylakoid functioning. However, MGDG in mammals has not received much attention, partly because of its relative scarcity in mammalian tissues. In addition, the biosynthetic pathway of MGDG in mammals has not been thoroughly analyzed, although some reports have suggested that UGT8, a ceramide galactosyltransferase, has the potential to catalyze MGDG biosynthesis.
View Article and Find Full Text PDFNicotinamide riboside targets mitochondrial unfolded protein response to reduce alcohol-induced damage in Kupffer cells.
J Pathol
January 2025
Department of Nutritional Sciences, University of Connecticut, Storrs, CT, USA.
Article Synopsis
- The study investigates how alcohol affects liver health by disrupting mitochondrial function and energy metabolism, focusing on inflammation and oxidative stress in Kupffer cells (liver macrophages).
- Researchers experimented with nicotinamide riboside (NR), a compound that may help counteract damage caused by ethanol exposure in these cells, showing that NR can improve mitochondrial function and reduce inflammation.
- The findings suggest that NR works by regulating a specific protein (ATF5) involved in the mitochondrial unfolded protein response (UPR), indicating its potential as a treatment for alcohol-related liver disease (ALD).
Exploring the reciprocal relationship between reflective and behavioural moral self-efficacy: An agentic perspective to hinder moral disengagement at work.
Int J Psychol
February 2025
Research Centre for Global Learning, Coventry University, Coventry, UK.
Moral self-efficacy refers to individuals' beliefs in their capability to effectively mobilise motivation, cognitive resources and strategic actions to achieve moral performance particularly in challenging situations. We adopt the conceptualization of moral self-efficacy that encompasses both self-reflective and behavioural components. The self-reflective dimension pertains to one's perceived capability to reflect on past moral lapses, while the behavioural dimension involves one's perceived capability to regulate future moral conduct.
View Article and Find Full Text PDFParticipation among young people in the child protection system and how it relates to subsequent educational and employment outcomes.
Child Abuse Negl
September 2024
VIVE - The Danish Center for Social Science Research, Herluf Trolles Gade 11, DK-1052 Copenhagen K, Denmark. Electronic address:
Background: Previous research has shown that young people in the child protection system experience different levels of participation in decision-making on important issues. Nonetheless, researchers agree that children's participation in decision-making is likely to affect critical factors in their lives, such as educational and employment performance.
Objectives: This study aimed to examine (1) to what extent the level of participation in decision-making is related to this group of young people's subsequent education and employment, and (2) how the relation varies between different dimensions of the measure of participation.
A single-pass type I membrane protein, mannose-specific L-type lectin, potentially involved in the adhesion and invasion of Cryptosporidium parvum.
Parasite
August 2024
College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450046, Henan, PR China - International Joint Research Laboratory for Zoonotic Diseases of Henan, Zhengzhou 450046, Henan, PR China - Key Laboratory of Quality and Safety Control of Poultry Products, Ministry of Agriculture and Rural Affairs, Zhengzhou 450046, Henan, PR China.
Cryptosporidium is a globally distributed zoonotic protozoan parasite that can cause severe diarrhea in humans and animals. L-type lectins are carbohydrate-binding proteins involved in multiple pathways in animals and plants, including protein transportation, secretion, innate immunity, and the unfolded protein response signaling pathway. However, the biological function of the L-type lectins remains unknown in Cryptosporidium parvum.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!