% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Goretzki:598500,
author = {Goretzki, Benedikt and Wiedemann, Christoph and McCray,
Brett A. and Schäfer, Stefan L. and Jansen, Jasmin and
Tebbe, Frederike and Mitrovic, Sarah-Ana and Nöth, Julia
and Cabezudo, Ainara Claveras and Donohue, Jack K. and
Jeffries, Cy and Steinchen, Wieland and Stengel, Florian and
Sumner, Charlotte J. and Hummer, Gerhard and Hellmich, Ute
A.},
title = {{C}rosstalk between regulatory elements in disordered
{TRPV}4 {N}-terminus modulates lipid-dependent channel
activity},
journal = {Nature Communications},
volume = {14},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {PUBDB-2023-06835},
pages = {4165},
year = {2023},
abstract = {Intrinsically disordered regions (IDRs) are essential for
membrane receptor regulation but often remain unresolved in
structural studies. TRPV4, a member of the TRP vanilloid
channel family involved in thermo- and osmosensation, has a
large N-terminal IDR of approximately 150 amino acids. With
an integrated structural biology approach, we analyze the
structural ensemble of the TRPV4 IDR and the network of
antagonistic regulatory elements it encodes. These modulate
channel activity in a hierarchical lipid-dependent manner
through transient long-range interactions. A highly
conserved autoinhibitory patch acts as a master regulator by
competing with PIP2 binding to attenuate channel activity.
Molecular dynamics simulations show that loss of the
interaction between the PIP2-binding site and the membrane
reduces the force exerted by the IDR on the structured core
of TRPV4. This work demonstrates that IDR structural
dynamics are coupled to TRPV4 activity and highlights the
importance of IDRs for TRP channel function and regulation.},
cin = {EMBL / EMBL-User / DOOR ; HAS-User},
ddc = {500},
cid = {I:(DE-H253)EMBL-20120731 / I:(DE-H253)EMBL-User-20120814 /
I:(DE-H253)HAS-User-20120731},
pnm = {6G3 - PETRA III (DESY) (POF4-6G3) / DFG project 390713860 -
EXC 2051: Balance of the Microverse (390713860)},
pid = {G:(DE-HGF)POF4-6G3 / G:(GEPRIS)390713860},
experiment = {EXP:(DE-H253)P-P12-20150101},
typ = {PUB:(DE-HGF)16},
pubmed = {37443299},
UT = {WOS:001030405300023},
doi = {10.1038/s41467-023-39808-4},
url = {https://bib-pubdb1.desy.de/record/598500},
}