The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
On the thermodynamic stability of a charged arginine side chain in a transmembrane helix
Open accessAbstract
Biological membranes consist of bilayer arrangements of lipids forming a hydrophobic core that presents a physical barrier to all polar and charged molecules. This long-held notion has recently been challenged by biological translocon-based experiments that report small apparent free energies to insert charged side chains near the center of a transmembrane (TM) helix. We have carried out fully atomistic simulations to provide the free-energy profile for moving a TM helix containing a protonated Arg side chain across a lipid bilayer. Our results reveal the fundamental thermodynamics governing the stability of charged side chains in membranes and the microscopic interactions involved. Despite local membrane deformations, where large amounts of water and lipid head groups are pulled into the bilayer to interact with Arg, the free-energy barrier is 17 kcal/mol. We provide a rationale for the differences in our microscopic free energies and cell biological experiments using free-energy calculations that indicate that a protonated Arg at the central residue of a TM helix of the Leader peptidase might reside close to the interface and not at the membrane center. Our findings have implications for the gating mechanisms of voltage-gated ion channels, suggesting that movements of protonated Arg residues through the membrane will be prohibited.
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Cites
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Cited by
Lipids on the move: Simulations of membrane pores, domains, stalks and curves
Marrink, S. J., de Vries, A. H., & Tieleman, D. P. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.10.006 · Cited by 440
Molecular Dynamics Simulations of Membrane Permeability
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Muller, M. P., Jiang, T., Sun, C., Lihan, M., Pant, S., Mahinthichaichan, P., Trifan, A., & Tajkhorshid, E. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00608 · Cited by 282
Transfer of Arginine into Lipid Bilayers Is Nonadditive
MacCallum, J. L., Bennett, W. F. D., & Tieleman, D. P. (2011) · Biophysical Journal · doi:10.1016/j.bpj.2011.05.038 · Cited by 101
Luo, W., & Hong, M. (2010) · Journal of the American Chemical Society · doi:10.1021/ja9096219 · Cited by 90
Metadata
- Authors
- Dorairaj, S., & Allen, T. W.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-03-20
- Volume
- 104
- Issue
- 12
- Pages
- 4943-4948
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2152270594
- Cited by
- 265
- References
- 46
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- green
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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