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Backbone Hydrogen Bond Energies in Membrane Proteins Are Insensitive to Large Changes in Local Water Concentration
journal contribution
posted on 2020-03-17, 14:39 authored by Henry
J. Lessen, Ananya Majumdar, Karen G. FlemingA hallmark
feature of biological lipid bilayer structure is a depth-dependent
polarity gradient largely resulting from the change in water concentration
over the angstrom length scale. This gradient is particularly steep
as it crosses the membrane interfacial regions where the water concentration
drops at least a million-fold along the direction of the bilayer normal.
Although local water content is often assumed to be a major determinant
of membrane protein stability, the effect of the water-induced polarity
gradient upon backbone hydrogen bond strength has not been systematically
investigated. We addressed this question by measuring the free energy
change for a number of backbone hydrogen bonds in the transmembrane
protein OmpW. These values were obtained at 33 backbone amides from
hydrogen/deuterium fractionation factors by nuclear magnetic resonance
spectroscopy. We surprisingly found that OmpW backbone hydrogen bond
energies do not vary over a wide range of water concentrations that
are characteristic of the solvation environment in the bilayer interfacial
region. We validated the interpretation of our results by determining
the hydrodynamic and solvation properties of our OmpW-micelle complex
using analytical ultracentrifugation and molecular dynamics simulations.
The magnitudes of the backbone hydrogen bond free energy changes in
our study are comparable to those observed in water-soluble proteins,
the H-segment of the leader peptidase helix used in the von Heijne
and White biological scale experiments, and several interfacial peptides.
Our results agree with those reported for the transmembrane α-helical
portion of the amyloid precursor protein after the latter values were
adjusted for kinetic isotope effects. Overall, our work suggests that
backbone hydrogen bonds provide modest thermodynamic stability to
membrane protein structures and that many amides are unaffected by
dehydration within the bilayer.
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Keywords
amyloid precursor proteindepth-dependent polarity gradient33 backbone amidestransmembrane protein OmpWOmpW backbone hydrogen bond energieswater concentrationangstrom length scaleBackbone Hydrogen Bond Energiestransmembrane α- helical portionmembrane protein stabilityLocal Water Concentrationbackbone hydrogen bond strengthmembrane protein structuresleader peptidase helixbackbone hydrogen bondslipid bilayer structurewater-induced polarity gradientbackbone hydrogen bond
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