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@ARTICLE{Risi:836818,
author = {Risi, Cristina and Eisner, Jamie and Belknap, Betty and
Heeley, David H. and White, Howard D. and Schröder, Gunnar
and Galkina, Vitold E.},
title = {{C}a2+-induced movement of tropomyosin on native cardiac
thin filaments revealed by cryoelectron microscopy},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {114},
issn = {0027-8424},
address = {Washington, DC},
publisher = {National Acad. of Sciences},
reportid = {FZJ-2017-05860},
pages = {6782-6787},
year = {2017},
abstract = {Muscle contraction relies on the interaction of myosin
motors with F-actin, which is regulated through a
translocation of tropomyosin by the troponin complex in
response to Ca2+ The current model of muscle regulation
holds that at relaxing (low-Ca2+) conditions tropomyosin
blocks myosin binding sites on F-actin, whereas at
activating (high-Ca2+) conditions tropomyosin translocation
only partially exposes myosin binding sites on F-actin so
that binding of rigor myosin is required to fully activate
the thin filament (TF). Here we used a single-particle
approach to helical reconstruction of frozen hydrated native
cardiac TFs under relaxing and activating conditions to
reveal the azimuthal movement of the tropomyosin on the
surface of the native cardiac TF upon Ca2+ activation. We
demonstrate that at either relaxing or activating conditions
tropomyosin is not constrained in one structural state, but
rather is distributed between three structural positions on
the surface of the TF. We show that two of these tropomyosin
positions restrain actomyosin interactions, whereas in the
third position, which is significantly enhanced at high
Ca2+, tropomyosin does not block myosin binding sites on
F-actin. Our data provide a structural framework for the
enhanced activation of the cardiac TF over the skeletal TF
by Ca2+ and lead to a mechanistic model for the regulation
of the cardiac TF.},
cin = {ICS-6},
ddc = {000},
cid = {I:(DE-Juel1)ICS-6-20110106},
pnm = {551 - Functional Macromolecules and Complexes (POF3-551)},
pid = {G:(DE-HGF)POF3-551},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000404108400058},
pubmed = {pmid:28607071},
doi = {10.1073/pnas.1700868114},
url = {https://juser.fz-juelich.de/record/836818},
}