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@ARTICLE{Sena:829376,
author = {Sena, Diniz M. and Cong, Xiaojing and Giorgetti, Alejandro
and Kless, Achim and Carloni, Paolo},
title = {{S}tructural heterogeneity of the $μ$-opioid receptor’s
conformational ensemble in the apo state},
journal = {Scientific reports},
volume = {7},
issn = {2045-2322},
address = {London},
publisher = {Nature Publishing Group},
reportid = {FZJ-2017-03089},
pages = {45761},
year = {2017},
abstract = {G-protein coupled receptors (GPCRs) are the largest and
most pharmaceutically relevant family of membrane proteins.
Here, fully unbiased, enhanced sampling simulations of a
constitutively active mutant (CAM) of a class A GPCR, the
μ-opioid receptor (μOR), demonstrates repeated transitions
between the inactive (IS) and active-like (AS-L) states. The
interconversion features typical activation/inactivation
patterns involving established conformational rearrangements
of conserved residues. By contrast, wild-type μOR remains
in IS during the same course of simulation, consistent with
the low basal activity of the protein. The simulations point
to an important role of residue W2936.48 at the “toggle
switch” in the mutation-induced constitutive activation.
Such role has been already observed for other CAMs of class
A GPCRs. We also find a significantly populated intermediate
state, rather similar to IS. Based on the remarkable accord
between simulations and experiments, we suggest here that
this state, which has escaped so far experimental
characterization, might constitute an early step in the
activation process of the apo μOR CAM.},
cin = {IAS-5 / INM-9},
ddc = {000},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {572 - (Dys-)function and Plasticity (POF3-572)},
pid = {G:(DE-HGF)POF3-572},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000398321200001},
pubmed = {pmid:28368046},
doi = {10.1038/srep45761},
url = {https://juser.fz-juelich.de/record/829376},
}