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Sedimentation Equilibrium of a Small Oligomer-forming Membrane Protein: Effect of Histidine Protonation on Pentameric Stability
Published on: April 2, 2015
Modest stabilization by most hydrogen-bonded side-chain interactions in membrane proteins
Nathan Hyunjoong Joh1, Andrew Min, Salem Faham
1Department of Chemistry and Biochemistry, UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute, USA.
Nature
|May 27, 2008
Summary
Hydrogen bonds in membrane proteins are weaker than previously thought, contributing only modestly to stability. This finding impacts our understanding of membrane protein folding, dynamics, and design.
Area of Science:
- Structural biology
- Biophysics
- Membrane protein research
Background:
- Hydrogen bonds are crucial for molecular interactions in structural biology.
- They are considered important in membrane environments due to low dielectric constants and lack of water competition.
- Polar residue substitutions are common disease-causing mutations in membrane proteins.
Purpose of the Study:
- To quantitatively test hydrogen-bond strength in large membrane proteins.
- To investigate the energetic contribution of interhelical side-chain hydrogen bonds in bacteriorhodopsin.
- To compare hydrogen bond characteristics in membrane proteins with soluble proteins.
Main Methods:
- Double-mutant cycle analysis was employed to measure hydrogen-bond contributions.
- Analysis of polar atom hydrogen-bonding partners in membrane protein cores.
- Statistical comparison of hydrogen bond lengths in soluble and membrane proteins.
Main Results:
- The average contribution of eight interhelical side-chain hydrogen bonds in bacteriorhodopsin was 0.6 kcal mol(-1).
- 4% of polar atoms in membrane protein non-polar core regions lacked hydrogen-bond partners.
- Buried hydrogen bond lengths in membrane proteins and soluble proteins were statistically identical.
Conclusions:
- Hydrogen-bonding interactions in membrane proteins are only modestly stabilizing.
- The weak stabilizing nature of these bonds should inform studies on membrane protein folding, dynamics, design, evolution, and function.
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