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dc.contributor.author
Mayer, Daniel
dc.contributor.supervisor
Schertler, Gebhard F. X.
dc.contributor.supervisor
Veprintsev, Dmitry
dc.contributor.supervisor
Meier, Beat
dc.contributor.supervisor
Damberger, Fred
dc.date.accessioned
2018-12-04T10:37:05Z
dc.date.available
2017-11-29T19:29:42Z
dc.date.available
2017-11-30T08:48:11Z
dc.date.available
2018-12-04T10:37:05Z
dc.date.issued
2017
dc.identifier.uri
http://hdl.handle.net/20.500.11850/215427
dc.identifier.doi
10.3929/ethz-b-000215427
dc.description.abstract
Arrestins are responsible for desensitization and internalization of activated, phosphorylated G protein-coupled receptors (GPCRs). Over the years, it became clear that they have the potential to activate certain signaling pathways which are independent from G protein signaling. The Arrestins family only comprises four members, but they interact with hundreds of GPCRs. Several studies suggested that downstream signaling by Arrestins is modulated by the phosphorylation patterns created by a small number of GPCR-specific kinases (GRKs). They are capable of introducing specific phosphorylation motifs on the cytosolic side of the receptor, which are either located at the third intracellular loop (ICL3) or at the C terminal tail. These phosphorylation motifs are ligand- and cell-dependent, which shows the highly dynamic regulatory potential of this system. Here, I used a library of synthetic phosphorylated peptides derived from the bovine Rhodopsin C-terminus to study their influence on the activation of Arrestins. I obtained a high resolution view of the conformational changes induced by different phosphorylation patterns in Arrestin-1 by NMR. In combination with other biophysical techniques, this allowed me to identify a pattern of two phosphorylations sites near the distal part of the C-terminus that are the KEY sites for the activation of Arrestins. Other motifs were found as well that may further modulate the conformational changes in Arrestins. This could explain how distinct phosphorylation patterns are capable of regulating a variety of downstream signaling events. I also showed that Arrestins differ in their potential to interact with phosphorylated C-tails which highlights the non-redundancy of β-Arrestins.
en_US
dc.format
application/pdf
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.subject
Arrestin
en_US
dc.subject
GPCR
en_US
dc.subject
phosphorylation barcode
en_US
dc.subject
phosphorylation sites
en_US
dc.title
Molecular basis for the recognition of the phosphorylation pattern in the C-terminal tail of GPCRs by arrestins
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2017-11-30
ethz.size
109 p.
en_US
ethz.code.ddc
DDC - DDC::5 - Science::570 - Life sciences
ethz.identifier.diss
24679
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02030 - Dep. Biologie / Dep. of Biology::03866 - Schertler, Gebhard (emeritus) / Schertler, Gebhard (emeritus)
en_US
ethz.date.deposited
2017-11-29T19:29:44Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.date.embargoend
2018-11-30
ethz.rosetta.installDate
2017-11-30T08:48:21Z
ethz.rosetta.lastUpdated
2023-02-06T16:40:15Z
ethz.rosetta.versionExported
true
ethz.COinS
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