Protein contents in biological membranes explain abnormal solvation of charged and polar residues
2009 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, Vol. 106, no 37, 15684-15689 p.Article in journal (Refereed) Published
Transmembrane helices are generally believed to insert into membranes based on their hydrophobicity. Nevertheless, there are important exceptions where polar or titratable residues have great functional importance, for instance the S4 helix of voltage-gated ion channels. It has been shown experimentally that insertion can be accomplished by hydrophobic counterbalance, which enabled biological hydrophobicity scales that predict an arginine insertion cost of only 2.5 kcal/mol, compared to 14.9 kcal/mol in cyklohexane. Previous simulations of pure bilayers have produced values close to the pure hydrocarbon, which has lead to vivid discussion about the experimental conditions. Here, we have performed computer simulations of models better mimicking biological membranes by explicitly including protein helices at mass fractions from 15% to 55%. This has a striking effect on the solvation free energy of arginine, which drops more than a factor of two even for purely hydrophobic extra helices. With some polar residues present, the solvation cost comes close to experimental observation around 30% mass fraction, and negligible at 40%. The effect is mainly due to the extra helices making it easier for arginine to retain hydration water, with increasing amounts at higher protein mass fraction. These results offer a possible explanation to the previous discrepancy between the in vivo hydrophobicity scale and computer simulations, and highlight the importance of the relatively high protein contents in biological membranes. While many membrane proteins are stable in pure bilayers, the simplified models might not be sufficiently accurate descriptions of insertion for polar or charged residues in biological membranes.
Place, publisher, year, edition, pages
2009. Vol. 106, no 37, 15684-15689 p.
membrane protein, lipid bilayer, protein mass fraction, free energy, solvation, insertion, molecular dynamics simulation
IdentifiersURN: urn:nbn:se:su:diva-27094DOI: 10.1073/pnas.0905394106ISI: 000269806600034OAI: oai:DiVA.org:su-27094DiVA: diva2:212610