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@ARTICLE{Loschwitz:1015356,
author = {Loschwitz, Jennifer and Steffens, Nora and Wang, Xue and
Schäffler, Moritz and Pfeffer, Klaus and Degrandi, Daniel
and Strodel, Birgit},
title = {{D}omain motions, dimerization, and membrane interactions
of the murine guanylate binding protein 2},
journal = {Scientific reports},
volume = {13},
number = {1},
issn = {2045-2322},
address = {[London]},
publisher = {Macmillan Publishers Limited, part of Springer Nature},
reportid = {FZJ-2023-03676},
pages = {679},
year = {2023},
abstract = {Guanylate-binding proteins (GBPs) are a group of GTPases
that are induced by interferon-γ and are crucial components
of cell-autonomous immunity against intracellular pathogens.
Here, we examine murine GBP2 (mGBP2), which we have
previously shown to be an essential effector protein for the
control of Toxoplasma gondii replication, with its
recruitment through the membrane of the parasitophorous
vacuole and its involvement in the destruction of this
membrane likely playing a role. The overall aim of our work
is to provide a molecular-level understanding of the mutual
influences of mGBP2 and the parasitophorous vacuole
membrane. To this end, we performed lipid-binding assays
which revealed that mGBP2 has a particular affinity for
cardiolipin. This observation was confirmed by fluorescence
microscopy using giant unilamellar vesicles of different
lipid compositions. To obtain an understanding of the
protein dynamics and how this is affected by GTP binding,
mGBP2 dimerization, and membrane binding, assuming that each
of these steps are relevant for the function of the protein,
we carried out standard as well as replica exchange
molecular dynamics simulations with an accumulated
simulation time of more than 30 μs. The main findings from
these simulations are that mGBP2 features a large-scale
hinge motion in its M/E domain, which is present in each of
the studied protein states. When bound to a
cardiolipin-containing membrane, this hinge motion is
particularly pronounced, leading to an up and down motion of
the M/E domain on the membrane, which did not occur on a
membrane without cardiolipin. Our prognosis is that this up
and down motion has the potential to destroy the membrane
following the formation of supramolecular mGBP2 complexes on
the membrane surface.},
cin = {IBI-7},
ddc = {600},
cid = {I:(DE-Juel1)IBI-7-20200312},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {36639389},
UT = {WOS:000968670400028},
doi = {10.1038/s41598-023-27520-8},
url = {https://juser.fz-juelich.de/record/1015356},
}