Change search
ReferencesLink to record
Permanent link

Direct link
Titratable amino acid solvation in lipid membranes as a function of protonation state.
Stockholm University.
Stockholm University.ORCID iD: 0000-0002-2734-2794
2009 (English)In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 113, no 1, 245-53 p.Article in journal (Refereed) Published
Abstract [en]

Knowledge about the insertion and stabilization of membrane proteins is a key step toward understanding their function and enabling membrane protein design. Transmembrane helices are normally quite hydrophobic so as to efficiently insert into membranes, but there are many exceptions with polar or titratable residues. An obvious example is the S4 helices of voltage-gated ion channels with up to 4 arginines, leading to vivid discussion about whether such helices can insert spontaneously, and if so, what their conformation, protonation state, and cost of insertion really are. To address this question, we have determined geometric and energetic solvation properties for different protonation states of the titrateable amino acids, including hydration, side chain orientation, free energy profiles, and effects on the membrane thickness. As expected, charged states are significantly more expensive to insert (8-16 kcal/mol) than neutral variants (1-3 kcal/mol). Although both sets of values exhibit quite high relative correlation with experimental in vivo hydrophobicity scales, the magnitudes of the in vivo hydrophobicity scales are much lower and strikingly appears as a compressed version of the calculated values. This agrees well with computational studies on longer lipids but results in an obvious paradox: the differences between in vivo insertion and simulations cannot be explained by methodological differences in force fields, possible limited hydrophobic thickness of the endoplasmic reticulum (ER) membrane, or parameters; even anionic lipid head groups (PG) only have limited effect on charged side chains, and virtually none for hydrophobic ones. This leads us to propose a model for in vivo insertion that could reconcile these differences and explain the correlation: if there are considerable hydrophobic barriers inside the translocon, the experimental reference state for the solvation free energy when comparing insertion/translocation in vivo would be quite close to the bilayer environment rather than water.

Place, publisher, year, edition, pages
2009. Vol. 113, no 1, 245-53 p.
National Category
Biophysics Bioinformatics and Systems Biology Theoretical Chemistry
URN: urn:nbn:se:kth:diva-82617DOI: 10.1021/jp8048873ISI: 000262167800031PubMedID: 19118487OAI: diva2:498486
QC 20120220Available from: 2012-02-12 Created: 2012-02-12 Last updated: 2012-02-20Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Lindahl, Erik
In the same journal
Journal of Physical Chemistry B
BiophysicsBioinformatics and Systems BiologyTheoretical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 12 hits
ReferencesLink to record
Permanent link

Direct link