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Cholesterol–Protein Interaction: Methods and Cholesterol Reporter Molecules

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Cholesterol Binding and Cholesterol Transport Proteins:

Part of the book series: Subcellular Biochemistry ((SCBI,volume 51))

Abstract

Cholesterol is a major constituent of the plasma membrane in eukaryotic cells. It regulates the physical state of the phospholipid bilayer and is crucially involved in the formation of membrane microdomains. Cholesterol also affects the activity of several membrane proteins, and is the precursor for steroid hormones and bile acids. Here, methods are described that are used to explore the binding and/or interaction of proteins to cholesterol. For this purpose, a variety of cholesterol probes bearing radio-, spin-, photoaffinity- or fluorescent labels are currently available. Examples of proven cholesterol binding molecules are polyene compounds, cholesterol-dependent cytolysins, enzymes accepting cholesterol as substrate, and proteins with cholesterol binding motifs. Main topics of this report are the localization of candidate membrane proteins in cholesterol-rich microdomains, the issue of specificity of cholesterol– protein interactions, and applications of the various cholesterol probes for these studies.

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Abbreviations

ACAT:

acyl-coenzyme A:cholesterol acyltransferase

BCθ-toxin:

a biotinylated and carlsberg protease-nicked derivative of perfringolysin O

Benzophenone-cholesterol:

22-(p-benzoylphenoxy)-23,24-bisnorcholan-5-en-3β-ol

Bodipy:

boron dipyrromethene(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diazara-s-indacene)

CCKBR:

cholecystokinin receptor type B

CCM:

cholesterol consensus motif

CDCs:

cholesterol-dependent cytolysins

CRAC:

cholesterol recognition/interaction amino acid consensus

DIG, (= DRM):

detergent-insoluble (= detergent resistant) glycosphingolipid-enriched membrane domains

GPCR:

G protein coupled receptor

HDL:

high-density lipoprotein

HPβCD:

2-Hydroxypropyl)-β-cyclodextrin

5HT1A:

5-hydroxytryptamine 1A

LDL:

low-density lipoprotein

LDM:

low-density microdomains

MβCD:

methyl-β-cyclodextrin

22-NBD Cholesterol:

22-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-23,24-bisnor-5-cholen-3β-ol

25-NBD Cholesterol:

25-[N-[(7-nitro-2-1,3-benzoxadiazol-4-yl)methyl]amino]-27-norcholesterol

NMR:

nuclear magnetic resonance

NPC:

Niemann-Pick C

OTR:

oxytocin receptor

PBR:

peripheral benzodiazepine receptor (= TSPO)

SCAP:

SREBP cleavage activating protein

SREBP:

sterol regulatory element binding protein

SSD:

sterol sensing domain

StAR:

steroid acute regulatory protein

START:

StAR related lipid transfer

TSPO:

mitochondrial translocator protein (18 kDa) (= PBR)

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Acknowledgements

I thank Christa Wolpert for technical assistance and Falk Fahrenholz, Katja Gehrig-Burger, Volker Wiegand, Conny Trossen, and Julian Reitz for discussions and cooperations in cholesterol research over recent years.

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  1. Institut für Biochemie, Johannes Gutenberg-Universität, Johann-Joachim-Becherweg 30, Mainz, Germany

    Gerald Gimpl

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    J. Robin Harris

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Gimpl, G. (2010). Cholesterol–Protein Interaction: Methods and Cholesterol Reporter Molecules. In: Harris, J. (eds) Cholesterol Binding and Cholesterol Transport Proteins:. Subcellular Biochemistry, vol 51. Springer, Dordrecht. https://doi.org/10.1007/978-90-481-8622-8_1

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