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@ARTICLE{Viegas:866585,
author = {Viegas, Aldino and Yin, Dongsheng M. and Borggräfe, Jan
and Viennet, Thibault and Falke, Marcel and Schmitz, Anton
and Famulok, Michael and Etzkorn, Manuel},
title = {{M}olecular {A}rchitecture of a {N}etwork of {P}otential
{I}ntracellular {EGFR} {M}odulators {I}nvolving the
{J}uxtamembrane {S}egment, {ARNO}, {P}hospholipids and
{C}a{M}},
journal = {Structure},
volume = {28},
issn = {0969-2126},
address = {Cambridge, Mass.},
publisher = {Cell Press},
reportid = {FZJ-2019-05668},
pages = {54-62},
year = {2020},
abstract = {Signaling of the Epidermal growth factor receptors (EGFRs)
is a central cellular element and its dysregulation is
related to a number of severe diseases. While ligand binding
to the extracellular domain is the receptor’s most obvious
regulatory element, also intracellular factors can act as
modulators of EGFR activity. The juxtamembrane (JM) segment
of the EGFR seems to be a key interaction interface of these
cytoplasmic factors. However, very few JM-interacting
molecules have been identified so far and even fewer is
known about the molecular mechanism underlying JM-targeted
receptor modulation. Here we report ARNO as a new EGFR-JM
binding protein and provide high-resolution insights into
its mode of interaction. We obtain comparable insights also
for the known interaction partners Calmodulin and
phospholipid bilayers containing different lipid
compositions. Our results show clear similarities and
distinct differences in each binding mode. Furthermore, we
show that each interaction can be modulated by a set of
additional orthogonal factors generating a distinctly
regulated competitive network of possible EGFR modulators
acting on the intracellular domain of the receptor. This
newly identified interaction network and the obtained
insights into the underlaying molecular mechanism may foster
future EGFR-targeted therapeutic strategies.},
cin = {ICS-6},
ddc = {540},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
doi = {10.2139/ssrn.3441425},
url = {https://juser.fz-juelich.de/record/866585},
}