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@ARTICLE{MiasLucquin:867581,
author = {Mias-Lucquin, Dominique and Dos Santos Morais, Raphael and
Chéron, Angélique and Lagarrigue, Mélanie and Winder,
Steve J. and Chenuel, Thomas and Pérez, Javier and Appavou,
Marie-Sousai and Martel, Anne and Alviset, Guillaume and Le
Rumeur, Elisabeth and Combet, Sophie and Hubert,
Jean-François and Delalande, Olivier},
title = {{H}ow the central domain of dystrophin acts to bridge
{F}-actin to sarcolemmal lipids},
journal = {Journal of structural biology},
volume = {209},
issn = {1047-8477},
address = {San Diego, Calif.},
publisher = {Elsevier},
reportid = {FZJ-2019-06204},
pages = {107411 -},
year = {2020},
abstract = {Dystrophin is a large intracellular protein that prevents
sarcolemmal ruptures by providing a mechanical link between
the intracellular actin cytoskeleton and the transmembrane
dystroglycan complex. Dystrophin deficiency leads to the
severe muscle wasting disease Duchenne Muscular Dystrophy
and the milder allelic variant, Becker Muscular Dystrophy
(DMD and BMD). Previous work has shown that concomitant
interaction of the actin binding domain 2 (ABD2) comprising
spectrin like repeats 11 to 15 (R11-15) of the central
domain of dystrophin, with both actin and membrane lipids,
can greatly increase membrane stiffness. Based on a
combination of SAXS and SANS measurements, mass spectrometry
analysis of cross-linked complexes and interactive
low-resolution simulations, we explored in vitro the
molecular properties of dystrophin that allow the formation
of ABD2-F-actin and ABD2-membrane model complexes. In
dystrophin we identified two subdomains interacting with
F-actin, one located in R11 and a neighbouring region in R12
and another one in R15, while a single lipid binding domain
was identified at the C-terminal end of R12. Relative
orientations of the dystrophin central domain with F-actin
and a membrane model were obtained from docking simulation
under experimental constraints. SAXS-based models were then
built for an extended central subdomain from R4 to R19,
including ABD2. Overall results are compatible with a
potential F-actin/dystrophin/membrane lipids ternary
complex. Our description of this selected part of the
dystrophin associated complex bridging muscle cell membrane
and cytoskeleton opens the way to a better understanding of
how cell muscle scaffolding is maintained through this
essential protein.},
cin = {JCNS-FRM-II / JCNS-1 / MLZ},
ddc = {540},
cid = {I:(DE-Juel1)JCNS-FRM-II-20110218 /
I:(DE-Juel1)JCNS-1-20110106 / I:(DE-588b)4597118-3},
pnm = {6G4 - Jülich Centre for Neutron Research (JCNS) (POF3-623)
/ 6G15 - FRM II / MLZ (POF3-6G15)},
pid = {G:(DE-HGF)POF3-6G4 / G:(DE-HGF)POF3-6G15},
experiment = {EXP:(DE-MLZ)KWS1-20140101 / EXP:(DE-MLZ)KWS2-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:31689503},
UT = {WOS:000507695200016},
doi = {10.1016/j.jsb.2019.107411},
url = {https://juser.fz-juelich.de/record/867581},
}