dc.contributor.author |
Prokop, Susanne Clara |
|
dc.contributor.author |
Perry NA |
|
dc.contributor.author |
Vishnivetskiy SA |
|
dc.contributor.author |
Tóth, András |
|
dc.contributor.author |
Inoue A |
|
dc.contributor.author |
Milligan G |
|
dc.contributor.author |
Iverson TM |
|
dc.contributor.author |
Hunyady, László |
|
dc.contributor.author |
Gurevich VV |
|
dc.date.accessioned |
2018-10-02T08:07:22Z |
|
dc.date.available |
2018-10-02T08:07:22Z |
|
dc.date.issued |
2017 |
|
dc.identifier |
85018304504 |
|
dc.identifier.citation |
pagination=98-107;
journalVolume=36;
journalTitle=CELLULAR SIGNALLING; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/4784 |
|
dc.identifier.uri |
doi:10.1016/j.cellsig.2017.04.021 |
|
dc.description.abstract |
Non-visual arrestins interact with hundreds of different G protein-coupled receptors (GPCRs). Here we show that by introducing mutations into elements that directly bind receptors, the specificity of arrestin-3 can be altered. Several mutations in the two parts of the central "crest" of the arrestin molecule, middle-loop and C-loop, enhanced or reduced arrestin-3 interactions with several GPCRs in receptor subtype and functional state-specific manner. For example, the Lys139Ile substitution in the middle-loop dramatically enhanced the binding to inactive M2 muscarinic receptor, so that agonist activation of the M2 did not further increase arrestin-3 binding. Thus, the Lys139Ile mutation made arrestin-3 essentially an activation-independent binding partner of M2, whereas its interactions with other receptors, including the beta2-adrenergic receptor and the D1 and D2 dopamine receptors, retained normal activation dependence. In contrast, the Ala248Val mutation enhanced agonist-induced arrestin-3 binding to the beta2-adrenergic and D2 dopamine receptors, while reducing its interaction with the D1 dopamine receptor. These mutations represent the first example of altering arrestin specificity via enhancement of the arrestin-receptor interactions rather than selective reduction of the binding to certain subtypes. |
|
dc.relation.ispartof |
urn:issn:0898-6568 |
|
dc.title |
Differential manipulation of arrestin-3 binding to basal and agonist-activated G protein-coupled receptors. |
|
dc.type |
Journal Article |
|
dc.date.updated |
2018-02-14T13:38:33Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
3222502 |
|
dc.identifier.wos |
000405044000010 |
|
dc.identifier.pubmed |
28461104 |
|
dc.contributor.department |
SE/AOK/I/Élettani Intézet |
|
dc.contributor.institution |
Semmelweis Egyetem |
|