Phytochemicals perturb membranes and promiscuously alter protein function.

TitlePhytochemicals perturb membranes and promiscuously alter protein function.
Publication TypeJournal Article
Year of Publication2014
AuthorsIngólfsson HI, Thakur P, Herold KF, E Hobart A, Ramsey NB, Periole X, de Jong DH, Zwama M, Yilmaz D, Hall K, Maretzky T, Hemmings HC, Blobel C, Marrink SJ, Koçer A, Sack JT, Andersen OS
JournalACS Chem Biol
Date Published2014 Aug 15
KeywordsCell Membrane, Membrane Proteins, Molecular Dynamics Simulation, Phytochemicals

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.

Alternate JournalACS Chem. Biol.
PubMed ID24901212
PubMed Central IDPMC4136704
Grant List5P30GM092328-02 / GM / NIGMS NIH HHS / United States
GM0213420-35S1 / GM / NIGMS NIH HHS / United States
GM58055 / GM / NIGMS NIH HHS / United States
R01 GM021342 / GM / NIGMS NIH HHS / United States
R01 GM021342 / GM / NIGMS NIH HHS / United States
R01 GM058055 / GM / NIGMS NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States