Membrane proteins play crucial roles in various physiological processes, including molecule transport across membranes, cell communication, and signal transduction. Approximately 60% of known drug targets are membrane proteins. There is a significant need to deeply understand the working mechanism of membrane proteins in detail, which is a challenging work due to the lack of available membrane structures and their large spatial scale. Membrane proteins carry out vital physiological functions through conformational changes. In the current study, we utilized a coarse-grained (CG) model to investigate three representative membrane protein systems: the TMEM16A channel, the family C GPCRs mGlu2 receptor, and the P4-ATPase phospholipid transporter. We constructed the reaction pathway of conformational changes between the two-end structures. Energy profiles and energy barriers were calculated. These data could provide reasonable explanations for TMEM16A activation, the mGlu2 receptor activation process, and P4-ATPase phospholipid transport. Although they all belong to the members of membrane proteins, they behave differently in terms of energy. Our work investigated the working mechanism of membrane proteins and could give novel insights into other membrane protein systems of interest.
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http://dx.doi.org/10.3390/membranes12070694 | DOI Listing |
Front Biosci (Landmark Ed)
January 2025
Department of Neurology, Jinshan Hospital, Fudan University, 201508 Shanghai, China.
Background: Neuronal cholesterol deficiency may contribute to the synaptopathy observed in Alzheimer's disease (AD). However, the underlying mechanisms remain poorly understood. Intact synaptic vesicle (SV) mobility is crucial for normal synaptic function, whereas disrupted SV mobility can trigger the synaptopathy associated with AD.
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January 2025
Division of Molecular Psychiatry, Center of Mental Health, University of Hospital Würzburg, 97080 Würzburg, Germany.
Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).
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January 2025
Department of Cardiovascular Medicine, Binzhou Medical University Hospital, 256603 Binzhou, Shandong, China.
Background: Cellular vacuolization is a commonly observed phenomenon under physiological and pathological conditions. However, the mechanisms underlying vacuole formation remain largely unresolved.
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Front Biosci (Landmark Ed)
January 2025
Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, 530021 Nanning, Guangxi, China.
Background: Rheumatic heart disease (RHD), which is caused mainly by Group A Streptococcus, leads to fibrotic damage to heart valves. Recently, endothelial‒mesenchymal transition (EndMT), in which activin plays an important role, has been shown to be an important factor in RHD valvular injury. However, the mechanism of activin activity and EndMT in RHD valvular injury is not clear.
View Article and Find Full Text PDFBr J Hosp Med (Lond)
January 2025
Birmingham School of Anaesthesia, West Midlands, UK.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are emerging as an important class of drugs in the management of Type 2 Diabetes Mellitus (T2DM) and obesity. There are rising concerns of pulmonary aspiration with these medications due to drug-induced gastroparesis. While definitive association is uncertain, it is essential to be prudent and manage these patients as per the current evidence and recommendations.
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