Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function
| Autor: | Djurre H. de Jong, Katherine C. Hall, Nicole Ramsey, Olaf S. Andersen, Karl F. Herold, Martijn Zwama, Pratima Thakur, Thorsten Maretzky, Carl P. Blobel, Armagan Kocer, Jon T. Sack, Helgi I. Ingólfsson, Siewert J. Marrink, Hugh C. Hemmings, E. Ashley Hobart, Duygu Yilmaz, Xavier Periole |
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| Přispěvatelé: | Molecular Dynamics, Enzymology, Molecular Neuroscience and Ageing Research (MOLAR) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Phytochemicals
ION-CHANNEL Molecular Dynamics Simulation Biochemistry Cell membrane 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine COARSE-GRAINED MODEL medicine Lipid bilayer LIPID-BILAYERS STATE NMR-SPECTROSCOPY GREEN TEA CATECHINS Ion channel 030304 developmental biology 0303 health sciences CATECHIN (-)-EPIGALLOCATECHIN GALLATE Bilayer Sodium channel Organic Chemistry Cell Membrane food and beverages Membrane Proteins General Medicine Articles Biological Sciences medicine.anatomical_structure INDUCED BILAYER DEFORMATIONS chemistry Membrane protein CHANNEL FUNCTION 030220 oncology & carcinogenesis Chemical Sciences Gramicidin Molecular Medicine Mechanosensitive channels MECHANOSENSITIVE CHANNEL GROWTH-FACTOR RECEPTOR |
| Zdroj: | ACS Chemical Biology ACS chemical biology, vol 9, iss 8 ACS chemical biology, 9(8), 1788-1798. AMER CHEMICAL SOC |
| ISSN: | 1554-8937 1554-8929 |
| Popis: | A wide variety of phytochemicals are consumed for their perceived health benefits. Many of these phytochemicals have been found to alter numerous cell functions, but the mechanisms underlying their biological activity tend to be poorly understood. Phenolic phytochemicals are particularly promiscuous modifiers of membrane protein function, suggesting that some of their actions may be due to a common, membrane bilayer-mediated mechanism. To test whether bilayer perturbation may underlie this diversity of actions, we examined five bioactive phenols reported to have medicinal value: capsaicin from chili peppers, curcumin from turmeric, EGCG from green tea, genistein from soybeans, and resveratrol from grapes. We find that each of these widely consumed phytochemicals alters lipid bilayer properties and the function of diverse membrane proteins. Molecular dynamics simulations show that these phytochemicals modify bilayer properties by localizing to the bilayer/solution interface. Bilayer-modifying propensity was verified using a gramicidin-based assay, and indiscriminate modulation of membrane protein function was demonstrated using four proteins: membrane-anchored metalloproteases, mechanosensitive ion channels, and voltage-dependent potassium and sodium channels. Each protein exhibited similar responses to multiple phytochemicals, consistent with a common, bilayer-mediated mechanism. Our results suggest that many effects of amphiphilic phytochemicals are due to cell membrane perturbations, rather than specific protein binding. |
| Databáze: | OpenAIRE |
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