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@ARTICLE{Schnke:16576,
author = {Schünke, S. and Stoldt, M. and Lecher, J. and Kaupp, U.B.
and Willbold, D.},
title = {{S}tructural insights into conformational changes of a
cyclic nucleotide-binding domain in solution from
{M}esorhizobium loti {K}1 channel},
journal = {Proceedings of the National Academy of Sciences of the
United States of America},
volume = {108},
issn = {0027-8424},
address = {Washington, DC},
publisher = {Academy},
reportid = {PreJuSER-16576},
pages = {6121 - 6126},
year = {2011},
note = {This study was supported by a fellowship from the
International Research School BioStruct to S.S. and a
research grant from the Helmholtz-Gemeinschaft (Virtual
Institute of Structural Biology) to D.W.},
abstract = {Cyclic nucleotide-sensitive ion channels, known as HCN and
CNG channels, are activated by binding of ligands to a
domain (CNBD) located on the cytoplasmic side of the
channel. The underlying mechanisms are not well understood.
To elucidate the gating mechanism, structures of both the
ligand-free and -bound CNBD are required. Several crystal
structures of the CNBD from HCN2 and a bacterial CNG channel
(MloK1) have been solved. However, for HCN2, the cAMP-free
and -bound state did not reveal substantial structural
rearrangements. For MloK1, structural information for the
cAMP-free state has only been gained from mutant CNBDs.
Moreover, in the crystal, the CNBD molecules form an
interface between dimers, proposed to be important for
allosteric channel gating. Here, we have determined the
solution structure by NMR spectroscopy of the cAMP-free
wild-type CNBD of MloK1. A comparison of the solution
structure of cAMP-free and -bound states reveals large
conformational rearrangement on ligand binding. The two
structures provide insights on a unique set of
conformational events that accompany gating within the
ligand-binding site.},
keywords = {Alphaproteobacteria: metabolism / Crystallography, X-Ray /
Cyclic AMP: chemistry / Cyclic Nucleotide-Gated Cation
Channels: chemistry / Cyclic Nucleotide-Gated Cation
Channels: genetics / Mutation / Nuclear Magnetic Resonance,
Biomolecular / Protein Structure, Tertiary / Cyclic
Nucleotide-Gated Cation Channels (NLM Chemicals) / Cyclic
AMP (NLM Chemicals) / J (WoSType)},
cin = {ICS-6},
ddc = {000},
cid = {I:(DE-Juel1)ICS-6-20110106},
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:21430265},
pmc = {pmc:PMC3076860},
UT = {WOS:000289413600042},
doi = {10.1073/pnas.1015890108},
url = {https://juser.fz-juelich.de/record/16576},
}