Hydrogen bond strength in membrane proteins probed by time-resolved1H-detected solid-state NMR and MD simulations.
1H-detected solid-state NMR in combination with1H/2D exchange steps allows for the direct identification of very strong hydrogen bonds in membrane proteins. On the example of the membrane-embedded potassium channel KcsA, we quantify the longevity of such very strong hydrogen bonds by combining time-resolved1H-detected solid-state NMR experiments and molecular dynamics simulations. In particular, we show that the carboxyl-side chain of the highly conserved residue Glu51 is involved in ultra-strong hydrogen bonds, which are fully-water-exposed and yet stable for weeks. The astonishing stability of these hydrogen bonds is important for the structural integrity of potassium channels, which we further corroborate by computational studies.
NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Utrecht University, Pandualaan 8, 3584 CH Utrecht, The Netherlands.
João
J
Medeiros-Silva
NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Utrecht University, Pandualaan 8, 3584 CH Utrecht, The Netherlands.
Shehrazade
S
Jekhmane
NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Utrecht University, Pandualaan 8, 3584 CH Utrecht, The Netherlands.
Marc
M
Baldus
NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Department of Chemistry, Utrecht University, Pandualaan 8, 3584 CH Utrecht, The Netherlands. Electronic address: m.h.weingarth@uu.nl.
Markus
M
Weingarth
D000595:Amino Acid Sequence; D006860:Hydrogen Bonding; D008565:Membrane Proteins / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011487:Protein Conformation; D013997:Time Factors
D008565:Membrane Proteins