کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2552046 1560704 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Use of plasmon waveguide resonance (PWR) spectroscopy for examining binding, signaling and lipid domain partitioning of membrane proteins
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Use of plasmon waveguide resonance (PWR) spectroscopy for examining binding, signaling and lipid domain partitioning of membrane proteins
چکیده انگلیسی

AimsDue to their anisotropic properties and other factors, it has been difficult to determine the conformational and dynamic properties of integral membrane proteins such as G-protein coupled receptors (GPCRs), growth factor receptors, ion channels, etc. in response to ligands and subsequent signaling. Herein a novel methodology is presented that allows such studies to be performed while maintaining the receptors in a membrane environment.Main methodPlasmon waveguide resonance (PWR) spectroscopy is a relatively new biophysical method which allows one to directly observe structural and dynamic changes which occur on interaction of GPCRs (and other integral membrane proteins) with ligands and signaling molecules. The delta opioid receptor (DOR) and its ligands serve as an excellent model system to illustrate the new insights into GPCR signaling that can be obtained by this method.Key findingsAmong our key findings are: 1) it is possible to obtain the following information directly and without any need for labels (radioactive, fluorescent, etc.): binding affinities, and the ability to distinguish between agonists, antagonists, inverse agonist, and partial agonists without a need for second messenger analysis; 2) it is possible to determine directly, again without a need for labels, G-protein binding to variously occupied or unoccupied DORs, and to determine which α-subtype is involved in allowing structurally different agonist ligands to have differential effects; 3) GTPγS binding can be examined directly; and 4) binding of the DOR with different ligands leads to differential segregation of the ligand-receptor complex into lipid rafts.SignificanceThe implications of these discoveries suggest a need to modify our current views of GPCR-ligand interactions and signaling.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 86, Issues 15–16, 10 April 2010, Pages 569–574
نویسندگان
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