Search: onr:"swepub:oai:research.chalmers.se:7b8209c2-cd1c-47ba-9508-a9915148d108" >
Equilibrium-Fluctua...
Equilibrium-Fluctuation Analysis for Interaction Studies between Natural Ligands and Single G Protein-Coupled Receptors in Native Lipid Vesicles
-
- Wahlsten, Olov, 1989 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Gunnarsson, Anders, 1981 (author)
- AstraZeneca AB
-
- Simonsson Nyström, Lisa, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
show more...
-
- Pace, Hudson, 1982 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
- Geschwindner, S. (author)
- AstraZeneca AB
-
- Höök, Fredrik, 1966 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
-
show less...
-
(creator_code:org_t)
- 2015-09-17
- 2015
- English.
-
In: Langmuir. - : American Chemical Society (ACS). - 1520-5827 .- 0743-7463. ; 31:39, s. 10774-10780
- Related links:
-
http://dx.doi.org/10...
-
show more...
-
https://doi.org/10.1...
-
https://research.cha...
-
show less...
Abstract
Subject headings
Close
- G protein-coupled receptors (GPCRs) constitute the most versatile family of cell-membrane receptors and have been increasingly identified as important mediators of many physiological functions. They also belong to one of the most central drug target classes, but current screening technologies are limited by the requirements of overexpression and stabilization of GPCRs. This calls for sensitivity-increased detection strategies preferably meeting single-molecule detection limits. This challenge is here addressed by employing total internal reflection fluorescence microscopy to characterize the interaction kinetics between CXCR3, a GPCR involved in inflammatory responses, and two of its chemokine ligands, CXCL10 and CXCL11. Fluorescence labeling of the lipid membrane, rather than the membrane protein itself, of GPCR-containing native vesicles, and immobilization of the corresponding ligand on the surface, enabled determination of the interaction kinetics using single-molecule equilibrium-fluctuation analysis. With a limit of detection of GPCR-containing vesicles in the low picomolar concentration regime, the results demonstrate the possibility to use inhibition in solution screening of high affinity ligands/drug candidates, which due to target-binding depletion of the inhibiting compounds is demanding using assays with more moderate detection limits.
Subject headings
- NATURVETENSKAP -- Fysik (hsv//swe)
- NATURAL SCIENCES -- Physical Sciences (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
-
Langmuir
(Search for host publication in LIBRIS)
To the university's database