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@ARTICLE{Zhang:8698,
author = {Zhang, J. and Baker, M.L. and Schröder, G.F. and Douglas,
N.R. and Reissmann, S. and Jakana, J. and Dougherty, M. and
Fu, C.J. and Levitt, M. and Ludtke, S.J. and Frydman, J. and
Chiu, W.},
title = {{M}echanism of folding chamber closure in a group {II}
chaperonin},
journal = {Nature},
volume = {463},
issn = {0028-0836},
address = {London [u.a.]},
publisher = {Nature Publising Group},
reportid = {PreJuSER-8698},
pages = {379 - 383},
year = {2010},
note = {We acknowledge the support of grants from the National
Institutes of Health through the Nanomedicine Development
Center Roadmap Initiative, Biomedical Technology Research
Center for Structural Biology in National Center for
Research Resources, Nanobiology Training Fellowship
administered by the Keck Center of the Gulf Coast Consortia
and the National Science Foundation.},
abstract = {Group II chaperonins are essential mediators of cellular
protein folding in eukaryotes and archaea. These oligomeric
protein machines, approximately 1 megadalton, consist of two
back-to-back rings encompassing a central cavity that
accommodates polypeptide substrates. Chaperonin-mediated
protein folding is critically dependent on the closure of a
built-in lid, which is triggered by ATP hydrolysis. The
structural rearrangements and molecular events leading to
lid closure are still unknown. Here we report four single
particle cryo-electron microscopy (cryo-EM) structures of
Mm-cpn, an archaeal group II chaperonin, in the
nucleotide-free (open) and nucleotide-induced (closed)
states. The 4.3 A resolution of the closed conformation
allowed building of the first ever atomic model directly
from the single particle cryo-EM density map, in which we
were able to visualize the nucleotide and more than $70\%$
of the side chains. The model of the open conformation was
obtained by using the deformable elastic network modelling
with the 8 A resolution open-state cryo-EM density
restraints. Together, the open and closed structures show
how local conformational changes triggered by ATP hydrolysis
lead to an alteration of intersubunit contacts within and
across the rings, ultimately causing a rocking motion that
closes the ring. Our analyses show that there is an
intricate and unforeseen set of interactions controlling
allosteric communication and inter-ring signalling, driving
the conformational cycle of group II chaperonins. Beyond
this, we anticipate that our methodology of combining single
particle cryo-EM and computational modelling will become a
powerful tool in the determination of atomic details
involved in the dynamic processes of macromolecular machines
in solution.},
keywords = {Adenosine Triphosphate: chemistry / Adenosine Triphosphate:
metabolism / Adenosine Triphosphate: pharmacology /
Allosteric Regulation / Binding Sites / Cryoelectron
Microscopy / Group II Chaperonins: chemistry / Group II
Chaperonins: metabolism / Group II Chaperonins:
ultrastructure / Hydrolysis: drug effects / Methanococcus:
chemistry / Models, Molecular / Protein Binding / Protein
Conformation: drug effects / Protein Folding / Protein
Subunits: chemistry / Protein Subunits: metabolism /
Structure-Activity Relationship / Protein Subunits (NLM
Chemicals) / Adenosine Triphosphate (NLM Chemicals) / Group
II Chaperonins (NLM Chemicals) / J (WoSType)},
cin = {ISB-3},
ddc = {070},
cid = {I:(DE-Juel1)VDB942},
pnm = {Funktion und Dysfunktion des Nervensystems / BioSoft:
Makromolekulare Systeme und biologische
Informationsverarbeitung},
pid = {G:(DE-Juel1)FUEK409 / G:(DE-Juel1)FUEK505},
shelfmark = {Multidisciplinary Sciences},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:20090755},
pmc = {pmc:PMC2834796},
UT = {WOS:000273748100049},
doi = {10.1038/nature08701},
url = {https://juser.fz-juelich.de/record/8698},
}