Supramolecular Organization and Functional Implications of K+ Channel Clusters in Membranes

The segregation of cellular surfaces in heterogeneous patches is considered to be a common motif in bacteria and eukaryotes that is underpinned by the observation of clustering and cooperative gating of signaling membrane proteins such as receptors or channels. Such processes could represent an impo...

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Published in:Angewandte Chemie International Edition 2017-10, Vol.56 (43), p.13222-13227
Main Authors: Visscher, Koen M., Medeiros‐Silva, João, Mance, Deni, Rodrigues, João P. G. L. M., Daniëls, Mark, Bonvin, Alexandre M. J. J., Baldus, Marc, Weingarth, Markus
Format: Article
Language:English
Subjects:
Bacteria
Cellular structure
Channel gating
Channels
Clustering
Communication
Communications
coupled gating
dynamic nuclear polarization
Eukaryotes
Functional morphology
ion channels
KcsA
Magnetic resonance spectroscopy
Membrane proteins
Membranes
NMR spectroscopy
Potassium channels
Proteins
Receptors
Solid state
solid-state NMR spectroscopy
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Summary:The segregation of cellular surfaces in heterogeneous patches is considered to be a common motif in bacteria and eukaryotes that is underpinned by the observation of clustering and cooperative gating of signaling membrane proteins such as receptors or channels. Such processes could represent an important cellular strategy to shape signaling activity. Hence, structural knowledge of the arrangement of channels or receptors in supramolecular assemblies represents a crucial step towards a better understanding of signaling across membranes. We herein report on the supramolecular organization of clusters of the K+ channel KcsA in bacterial membranes, which was analyzed by a combination of DNP‐enhanced solid‐state NMR experiments and MD simulations. We used solid‐state NMR spectroscopy to determine the channel–channel interface and to demonstrate the strong correlation between channel function and clustering, which suggests a yet unknown mechanism of communication between K+ channels. Multichannel communication: The anatomy of K+ channel clusters was dissected by combining DNP‐enhanced solid‐state NMR spectroscopy with large‐scale molecular dynamics simulations. The results discussed herein demonstrate that there is a correlation between ion channel clustering and function.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201705723