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@ARTICLE{Granzin:276150,
author = {Granzin, Joachim and Stadler, Andreas and Cousin, Anneliese
and Schlesinger, Ramona and Batra-Safferling, Renu},
title = {{S}tructural evidence for the role of polar core residue
{A}rg175 in arrestin activation},
journal = {Scientific reports},
volume = {5},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2015-06623},
pages = {15808},
year = {2015},
abstract = {Binding mechanism of arrestin requires photoactivation and
phosphorylation of the receptor protein rhodopsin, where the
receptor bound phosphate groups cause displacement of the
long C-tail ‘activating’ arrestin. Mutation of arginine
175 to glutamic acid (R175E), a central residue in the polar
core and previously predicted as the ‘phosphosensor’
leads to a pre-active arrestin that is able to terminate
phototransduction by binding to non-phosphorylated,
light-activated rhodopsin. Here, we report the first crystal
structure of a R175E mutant arrestin at 2.7 Å resolution
that reveals significant differences compared to the basal
state reported in full-length arrestin structures. These
differences comprise disruption of hydrogen bond network in
the polar core, and three-element interaction including
disordering of several residues in the receptor-binding
finger loop and the C-terminus (residues 361–404).
Additionally, R175E structure shows a 7.5° rotation of the
amino and carboxy-terminal domains relative to each other.
Consistent to the biochemical data, our structure suggests
an important role of R29 in the initial activation step of
C-tail release. Comparison of the crystal structures of
basal arrestin and R175E mutant provide insights into the
mechanism of arrestin activation, where binding of the
receptor likely induces structural changes mimicked as in
R175E.},
cin = {ICS-1 / Neutronenstreuung ; JCNS-1 / ICS-6},
ddc = {000},
cid = {I:(DE-Juel1)ICS-1-20110106 / I:(DE-Juel1)JCNS-1-20110106 /
I:(DE-Juel1)ICS-6-20110106},
pnm = {551 - Functional Macromolecules and Complexes (POF3-551) /
6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
/ 6215 - Soft Matter, Health and Life Sciences (POF3-621)},
pid = {G:(DE-HGF)POF3-551 / G:(DE-HGF)POF3-6G4 /
G:(DE-HGF)POF3-6215},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000363624600001},
doi = {10.1038/srep15808},
url = {https://juser.fz-juelich.de/record/276150},
}