Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 22, Pages 11908-11915Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2001083117
Keywords
molecular dynamics; gramicidin A; ultra-high field NMR; water wire; O-17 NMR
Categories
Funding
- NIH [AI023007, AI119178, GM122698, GM118091]
- Pukyong National University Research Abroad Fund in 2017 [C-D-2017-0984]
- NSF [DMR-1039938, DMR-0603042]
- NSF Division of Materials Research [DMR-1644779]
- State of Florida
- National Research Foundation of Korea [21A20130012185] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 O-17 NMR spectroscopy at 35.2 T (or 1,500 MHz for H-1) and computational studies. While backbone N-15 spectra clearly indicate structural symmetry between the two subunits, single site O-17 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 O-17 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+ ions bound at the two ends of the pore, thereby providing a simple explanation for an similar to 20-fold difference in K+ affinity between two binding sites that are similar to 24 A apart. The O-17 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 O-17 nucleus to its chemical environment.
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