Back to Search
Start Over
Functional stability of water wire-carbonyl interactions in an ion channel.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Jun 02; Vol. 117 (22), pp. 11908-11915. Date of Electronic Publication: 2020 May 15. - Publication Year :
- 2020
-
Abstract
- Water wires are critical for the functioning of many membrane proteins, as in channels that conduct water, protons, and other ions. Here, in liquid crystalline lipid bilayers under symmetric environmental conditions, the selective hydrogen bonding interactions between eight waters comprising a water wire and a subset of 26 carbonyl oxygens lining the antiparallel dimeric gramicidin A channel are characterized by <superscript>17</superscript> O NMR spectroscopy at 35.2 T (or 1,500 MHz for <superscript>1</superscript> H) and computational studies. While backbone <superscript>15</superscript> N spectra clearly indicate structural symmetry between the two subunits, single site <superscript>17</superscript> O labels of the pore-lining carbonyls report two resonances, implying a break in dimer symmetry caused by the selective interactions with the water wire. The <superscript>17</superscript> O shifts document selective water hydrogen bonding with carbonyl oxygens that are stable on the millisecond timescale. Such interactions are supported by density functional theory calculations on snapshots taken from molecular dynamics simulations. Water hydrogen bonding in the pore is restricted to just three simultaneous interactions, unlike bulk water environs. The stability of the water wire orientation and its electric dipole leads to opposite charge-dipole interactions for K <superscript>+</superscript> ions bound at the two ends of the pore, thereby providing a simple explanation for an ∼20-fold difference in K <superscript>+</superscript> affinity between two binding sites that are ∼24 Å apart. The <superscript>17</superscript> O NMR spectroscopy reported here represents a breakthrough in high field NMR technology that will have applications throughout molecular biophysics, because of the acute sensitivity of the <superscript>17</superscript> O nucleus to its chemical environment.<br />Competing Interests: The authors declare no competing interest.<br /> (Copyright © 2020 the Author(s). Published by PNAS.)
- Subjects :
- Binding Sites
Biophysical Phenomena
Cellular Microenvironment
Computational Biology
Hydrogen Bonding
Ion Channels metabolism
Lipid Bilayers chemistry
Lipid Bilayers metabolism
Models, Molecular
Oxygen Isotopes metabolism
Gramicidin chemistry
Ion Channels chemistry
Magnetic Resonance Spectroscopy methods
Water chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32414918
- Full Text :
- https://doi.org/10.1073/pnas.2001083117