Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

Helgi I Ingólfsson; Pratima Thakur; Karl F Herold; E. Ashley Hobart; Nicole B Ramsey; Xavier Periole; Djurre H de Jong; Martijn Zwama; Duygu Yilmaz; Katherine Hall; Thorsten Maretzky; Hugh C Hemmings; Carl Blobel; Siewert J Marrink; Armağan Koçer; Jon T Sack; Olaf S Andersen

doi:10.1021/cb500086e

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Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

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Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function

Helgi I Ingólfsson, Pratima Thakur, Karl F Herold, E. Ashley Hobart, Nicole B Ramsey, Xavier Periole, Djurre H de Jong, Martijn Zwama, Duygu Yilmaz, Katherine Hall, …

ACS chemical biology, Vol.9(8), pp.1788-1798

08/15/2014

DOI: 10.1021/cb500086e

PMCID: PMC4136704

PMID: 24901212

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Abstract

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.

Details

Title: Subtitle: Phytochemicals Perturb Membranes and Promiscuously Alter Protein Function
Creators: Helgi I Ingólfsson - Zernike Institute for Advanced Materials
Pratima Thakur - Dept. Physiology and Membrane Biology
Karl F Herold - Dept. Anesthesiology
E. Ashley Hobart - Dept. Anesthesiology
Nicole B Ramsey - Dept. Anesthesiology
Xavier Periole - Zernike Institute for Advanced Materials
Djurre H de Jong - Zernike Institute for Advanced Materials
Martijn Zwama - Zernike Institute for Advanced Materials
Duygu Yilmaz - Zernike Institute for Advanced Materials
Katherine Hall - Hospital for Special Surgery, New York, New York
Thorsten Maretzky - Hospital for Special Surgery, New York, New York
Hugh C Hemmings - Dept. Anesthesiology
Carl Blobel - Hospital for Special Surgery, New York, New York
Siewert J Marrink - Zernike Institute for Advanced Materials
Armağan Koçer - Zernike Institute for Advanced Materials
Jon T Sack - Dept. Physiology and Membrane Biology
Olaf S Andersen - Dept. Anesthesiology
Resource Type: Journal article
Publication Details: ACS chemical biology, Vol.9(8), pp.1788-1798
DOI: 10.1021/cb500086e
PMID: 24901212
PMCID: PMC4136704
NLM abbreviation: ACS Chem Biol
ISSN: 1554-8929
eISSN: 1554-8937
Publisher: American Chemical Society
Language: English
Date published: 08/15/2014
Academic Unit: Internal Medicine
Record Identifier: 9984094570502771

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