Publication

Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4

Pluhackova, K., Gahbauer, S., Kranz, F., Wassenaar, T. A. & Boeckmann, R. A., Nov-2016, In : PLoS Computational Biology. 12, 11, 25 p., 1005169.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Pluhackova, K., Gahbauer, S., Kranz, F., Wassenaar, T. A., & Boeckmann, R. A. (2016). Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4. PLoS Computational Biology, 12(11), [1005169]. https://doi.org/10.1371/journal.pcbi.1005169

Author

Pluhackova, Kristyna ; Gahbauer, Stefan ; Kranz, Franziska ; Wassenaar, Tsjerk A. ; Boeckmann, Rainer A. / Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4. In: PLoS Computational Biology. 2016 ; Vol. 12, No. 11.

Harvard

Pluhackova, K, Gahbauer, S, Kranz, F, Wassenaar, TA & Boeckmann, RA 2016, 'Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4', PLoS Computational Biology, vol. 12, no. 11, 1005169. https://doi.org/10.1371/journal.pcbi.1005169

Standard

Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4. / Pluhackova, Kristyna; Gahbauer, Stefan; Kranz, Franziska; Wassenaar, Tsjerk A.; Boeckmann, Rainer A.

In: PLoS Computational Biology, Vol. 12, No. 11, 1005169, 11.2016.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Pluhackova K, Gahbauer S, Kranz F, Wassenaar TA, Boeckmann RA. Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4. PLoS Computational Biology. 2016 Nov;12(11). 1005169. https://doi.org/10.1371/journal.pcbi.1005169


BibTeX

@article{140e2f84ae10403e85bd9839865bc965,
title = "Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4",
abstract = "G protein coupled receptors (GPCRs) allow for the transmission of signals across biological membranes. For a number of GPCRs, this signaling was shown to be coupled to prior dimerization of the receptor. The chemokine receptor type 4 (CXCR4) was reported before to form dimers and their functionality was shown to depend on membrane cholesterol. Here, we address the dimerization pattern of CXCR4 in pure phospholipid bilayers and in cholesterol-rich membranes. Using ensembles of molecular dynamics simulations, we show that CXCR4 dimerizes promiscuously in phospholipid membranes. Addition of cholesterol dramatically affects the dimerization pattern: cholesterol binding largely abolishes the preferred dimer motif observed for pure phospholipid bilayers formed mainly by transmembrane helices 1 and 7 (TM1/TM5-7) at the dimer interface. In turn, the symmetric TM3,4/TM3,4 interface is enabled first by intercalating cholesterol molecules. These data provide a molecular basis for the modulation of GPCR activity by its lipid environment.",
keywords = "COARSE-GRAINED MODEL, CRYSTAL-STRUCTURE, FORCE-FIELD, MOLECULAR-DYNAMICS, OPIOID RECEPTOR, BETA(2)-ADRENERGIC RECEPTOR, BIOMOLECULAR SIMULATIONS, HIV-1 CORECEPTOR, STRUCTURAL BASIS, BINDING-SITES",
author = "Kristyna Pluhackova and Stefan Gahbauer and Franziska Kranz and Wassenaar, {Tsjerk A.} and Boeckmann, {Rainer A.}",
year = "2016",
month = "11",
doi = "10.1371/journal.pcbi.1005169",
language = "English",
volume = "12",
journal = "PLoS Computational Biology",
issn = "1553-7358",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "11",

}

RIS

TY - JOUR

T1 - Dynamic Cholesterol-Conditioned Dimerization of the G Protein Coupled Chemokine Receptor Type 4

AU - Pluhackova, Kristyna

AU - Gahbauer, Stefan

AU - Kranz, Franziska

AU - Wassenaar, Tsjerk A.

AU - Boeckmann, Rainer A.

PY - 2016/11

Y1 - 2016/11

N2 - G protein coupled receptors (GPCRs) allow for the transmission of signals across biological membranes. For a number of GPCRs, this signaling was shown to be coupled to prior dimerization of the receptor. The chemokine receptor type 4 (CXCR4) was reported before to form dimers and their functionality was shown to depend on membrane cholesterol. Here, we address the dimerization pattern of CXCR4 in pure phospholipid bilayers and in cholesterol-rich membranes. Using ensembles of molecular dynamics simulations, we show that CXCR4 dimerizes promiscuously in phospholipid membranes. Addition of cholesterol dramatically affects the dimerization pattern: cholesterol binding largely abolishes the preferred dimer motif observed for pure phospholipid bilayers formed mainly by transmembrane helices 1 and 7 (TM1/TM5-7) at the dimer interface. In turn, the symmetric TM3,4/TM3,4 interface is enabled first by intercalating cholesterol molecules. These data provide a molecular basis for the modulation of GPCR activity by its lipid environment.

AB - G protein coupled receptors (GPCRs) allow for the transmission of signals across biological membranes. For a number of GPCRs, this signaling was shown to be coupled to prior dimerization of the receptor. The chemokine receptor type 4 (CXCR4) was reported before to form dimers and their functionality was shown to depend on membrane cholesterol. Here, we address the dimerization pattern of CXCR4 in pure phospholipid bilayers and in cholesterol-rich membranes. Using ensembles of molecular dynamics simulations, we show that CXCR4 dimerizes promiscuously in phospholipid membranes. Addition of cholesterol dramatically affects the dimerization pattern: cholesterol binding largely abolishes the preferred dimer motif observed for pure phospholipid bilayers formed mainly by transmembrane helices 1 and 7 (TM1/TM5-7) at the dimer interface. In turn, the symmetric TM3,4/TM3,4 interface is enabled first by intercalating cholesterol molecules. These data provide a molecular basis for the modulation of GPCR activity by its lipid environment.

KW - COARSE-GRAINED MODEL

KW - CRYSTAL-STRUCTURE

KW - FORCE-FIELD

KW - MOLECULAR-DYNAMICS

KW - OPIOID RECEPTOR

KW - BETA(2)-ADRENERGIC RECEPTOR

KW - BIOMOLECULAR SIMULATIONS

KW - HIV-1 CORECEPTOR

KW - STRUCTURAL BASIS

KW - BINDING-SITES

U2 - 10.1371/journal.pcbi.1005169

DO - 10.1371/journal.pcbi.1005169

M3 - Article

VL - 12

JO - PLoS Computational Biology

JF - PLoS Computational Biology

SN - 1553-7358

IS - 11

M1 - 1005169

ER -

ID: 65651881