Pathogenesis-related 10 (PR-10) proteins are involved in many aspects of plant biology but their molecular function is still unclear. They are related by sequence and structural homology to mammalian lipid transport and plant abscisic acid receptor proteins and are predicted to have cavities for ligand binding. Recently, three new members of the PR-10 family, the Fra a proteins, have been identified in strawberry, where they are required for the activity of the flavonoid biosynthesis pathway, which is essential for the development of color and flavor in fruits. Here, we show that Fra a proteins bind natural flavonoids with different selectivity and affinities in the low μm range. The structural analysis of Fra a 1 E and a Fra a 3-catechin complex indicates that loops L3, L5, and L7 surrounding the ligand-binding cavity show significant flexibility in the apo forms but close over the ligand in the Fra a 3-catechin complex. Our findings provide mechanistic insight on the function of Fra a proteins and suggest that PR-10 proteins, which are widespread in plants, may play a role in the control of secondary metabolic pathways by binding to metabolic intermediates.
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http://dx.doi.org/10.1074/jbc.M113.501528 | DOI Listing |
Nutrients
December 2024
Department of Experimental Medicine, Section of Biochemistry, University of Genova, Viale Benedetto XV 1, 16132 Genova, Italy.
Abscisic acid (ABA) is a hormone with a long evolutionary history, dating back to the earliest living organisms, of which modern (ABA-producing) cyanobacteria are likely descendants, which existed long before the separation of the plant and animal kingdoms, with a conserved role as signals regulating cell responses to environmental challenges. In mammals, along with the anti-inflammatory and neuroprotective function of ABA, nanomolar ABA regulates the metabolic response to glucose availability by stimulating glucose uptake in skeletal muscle and adipose tissue via an insulin-independent mechanism and increasing metabolic energy production and also dissipation in brown and white adipocytes. Chronic ABA intake of micrograms per Kg body weight improves blood glucose, lipids, and morphometric parameters (waist circumference and body mass index) in borderline subjects for prediabetes and metabolic syndrome.
View Article and Find Full Text PDFFEBS J
January 2025
Physics, Department of Molecular and Translational Medicine, University of Brescia, Italy.
Neutrophil elastase (NE) is released by activated neutrophils during an inflammatory response and exerts proteolytic activity on elastin and other extracellular matrix components. This protease is rapidly inhibited by the plasma serine protease inhibitor alpha-1-antitrypsin (AAT), and the importance of this protective activity on lung tissue is highlighted by the development of early onset emphysema in individuals with AAT deficiency. As a serpin, AAT presents a surface-exposed reactive centre loop (RCL) whose sequence mirrors the target protease specificity.
View Article and Find Full Text PDFSynaptic dysfunction is one of the earliest cellular defects observed in Alzheimer's disease (AD) and Parkinson's disease (PD), occurring before widespread protein aggregation, neuronal loss, and cognitive decline. While the field has focused on the aggregation of Tau and α-Synuclein (α-Syn), emerging evidence suggests that these proteins may drive presynaptic pathology even before their aggregation. Therefore, understanding the mechanisms by which Tau and α-Syn affect presynaptic terminals offers an opportunity for developing innovative therapeutics aimed at preserving synapses and potentially halting neurodegeneration.
View Article and Find Full Text PDFBrain Res Bull
January 2025
Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Xi'an 710061, China. Electronic address:
Neuromedin B (NMB) has potentially great impacts on the development of cardiovascular diseases by promoting hypertensive and sympatho-excitation effects. However, studies regarding the NMB function in paraventricular nucleus (PVN) are lacking. With selective neuromedin B receptor (NMBR) antagonist, BIM-23127, we aim to determine whether the blockade of NMB function in PVN could alleviate central inflammation and attenuate hypertensive responses.
View Article and Find Full Text PDFActa Neuropathol Commun
December 2024
Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute, KU Leuven, Leuven, Belgium.
The accumulation of abnormal phosphorylated Tau protein (pTau) in neurons of the brain is a pathological hallmark of Alzheimer's disease (AD). PTau pathology also occurs in the retina of AD cases. Accordingly, questions arise whether retinal pTau can act as a potential seed for inducing cerebral pTau pathology and whether retinal pTau pathology causes degeneration of retinal neurons.
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