TY  - JOUR
AU  - Schünke, S.
AU  - Stoldt, M.
AU  - Lecher, J.
AU  - Kaupp, U.B.
AU  - Willbold, D.
TI  - Structural insights into conformational changes of a cyclic nucleotide-binding domain in solution from Mesorhizobium loti K1 channel
JO  - Proceedings of the National Academy of Sciences of the United States of America
VL  - 108
SN  - 0027-8424
CY  - Washington, DC
PB  - Academy
M1  - PreJuSER-16576
SP  - 6121 - 6126
PY  - 2011
N1  - 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.
AB  - 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.
KW  - Alphaproteobacteria: metabolism
KW  - Crystallography, X-Ray
KW  - Cyclic AMP: chemistry
KW  - Cyclic Nucleotide-Gated Cation Channels: chemistry
KW  - Cyclic Nucleotide-Gated Cation Channels: genetics
KW  - Mutation
KW  - Nuclear Magnetic Resonance, Biomolecular
KW  - Protein Structure, Tertiary
KW  - Cyclic Nucleotide-Gated Cation Channels (NLM Chemicals)
KW  - Cyclic AMP (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:21430265
C2  - pmc:PMC3076860
UR  - <Go to ISI:>//WOS:000289413600042
DO  - DOI:10.1073/pnas.1015890108
UR  - https://juser.fz-juelich.de/record/16576
ER  -