Utrecht University

Biological Solid-State NMR

Utrecht University

K+ channels cluster in reference to their gating cycle

Using a combination of dynamic nuclear polarisation (DNP) enhanced solid-state NMR measurements in bacterial membranes and large-scale computer simulations, we could recently show that K+ channels aggregate and dissolve  in reference to their gating cycle, uncovering a hitherto unknown mechanism of functional coupling between K+ channels.

Check out the paper in  Angewandte Chemie 2017 - Visscher et al.

We are currently exploring  how cluster formation modulates the channel lipid microenvironment (manuscript in preparation).

The selectivity filter is subjected to slow dynamics on functional timescales

The selectivity filter of potassium channels is highly conserved throughout bacteria and eukaryotes. Using modern 1H-detected solid-state NMR, we demonstrate that the conductive selectivity  filter exhibits substantially increased slow microsecond motion. Such slow motion is on the same time-scale as thus far unexplained gating modes such as flickering.

Check out the paper in Angewandte Chemie 2016 - Medeiros-Silva et al.  

Buried water in K+ channels

Buried water molecules behind the selectivity filter act as 'gatekeepers', i.e., they are decisive for the conformational state of the inactivation gate/selectivity filter of K+ channels. This was first shown in an elegant computational paper by the group of Benoît Roux (Nature 2013). We have provided the first experimental evidence for the presence of these crucial buried water molecules behind the filter in membranes.

Check out the papers in JACS 2014  and Angewandte Chemie 2015

K+ channel - lipid interaction...

K+ channels are critically modulates by specific lipid interactions, however, such protein-lipid interactions are tricky to probe at high-resolution. By integrating solid-state NMR experiments, MD simulations, and single channel conductance measurements, we could show that anionic lipids critically modulate the activity of the KcsA K+ channel (see here for the paper in JACS 2013 Weingarth et al.).

Furthermore, using NMR and MD simulations, we could demonstrate that anionic lipids are important for the plasticity of K+ channels in reference to the gating mode (see here for the paper in PNAS 2013).