| 1. |
- Cournia, Zoe, et al.
(author)
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Membrane Protein Structure, Function, and Dynamics : a Perspective from Experiments and Theory
- 2015
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In: Journal of Membrane Biology. - : Springer. - 0022-2631 .- 1432-1424. ; 248:4, s. 611-640
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Journal article (peer-reviewed)abstract
- Membrane proteins mediate processes that are fundamental for the flourishing of biological cells. Membrane-embedded transporters move ions and larger solutes across membranes; receptors mediate communication between the cell and its environment and membrane-embedded enzymes catalyze chemical reactions. Understanding these mechanisms of action requires knowledge of how the proteins couple to their fluid, hydrated lipid membrane environment. We present here current studies in computational and experimental membrane protein biophysics, and show how they address outstanding challenges in understanding the complex environmental effects on the structure, function, and dynamics of membrane proteins.
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| 2. |
- Johansson, Anna CV, 1979-
(author)
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Solvation properties of proteins in membranes
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Knowledge about the insertion and stabilization of membrane proteins is a key step towards understanding their function and enabling membrane protein design. Transmembrane helices are normally quite hydrophobic to insert efficiently, but there are many exceptions with unfavorable polar or titratable residues. Since evolutionary conserved these amino acids are likely of paramount functional importance, e.g. the four arginines in the S4 voltage sensor helix of voltage-gated ion channels. This has lead to vivid discussion about their conformation, protonation state and cost of insertion. To address such questions, the main focus of this thesis has been membrane protein solvation in lipid bilayers, evaluated using molecular dynamics simulations methods.A main result is that polar and charged amino acids tend to deform the bilayer by pulling water/head-groups into the hydrophobic core to keep their hydrogen bonds paired, thus demonstrating the adaptiveness of the membrane to allow specific and quite complex solvation. In addition, this retained hydration suggests that the solvation cost is mainly due to entropy, not enthalpy loss. To further quantify solvation properties, free energy profiles were calculated for all amino acids in pure bilayers, with shapes correlating well with experimental in vivo values but with higher magnitudes. Additional profiles were calculated for different protonation states of the titratable amino acids, varying lipid composition and with transmembrane helices present in the bilayer. While the two first both influence solvation properties, the latter seems to be a critical aspect. When the protein fraction in the models resemble biological membranes, the solvation cost drops significantly - even to values compatible with experiment.In conclusion, by using simulation based methods I have been able to provide atomic scale explanations to experimental results, and in particular present a hypothesis for how the solvation of charged groups occurs.
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| 3. |
- Kotnik, Tadej, et al.
(author)
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Membrane Electroporation and Electropermeabilization : Mechanisms and Models
- 2019
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In: Annual Review of Biophysics, vol 48. - : Annual Reviews Inc.. - 1936-1238. - 9780824318482 ; , s. 63-91
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Book chapter (peer-reviewed)abstract
- Exposure of biological cells to high-voltage, short-duration electric pulses causes a transient increase in their plasma membrane permeability, allowing transmembrane transport of otherwise impermeant molecules. In recent years, large steps were made in the understanding of underlying events. Formation of aqueous pores in the lipid bilayer is now a widely recognized mechanism, but evidence is growing that changes to individual membrane lipids and proteins also contribute, substantiating the need for terminological distinction between electroporation and electropermeabilization. We first revisit experimental evidence for electrically induced membrane permeability, its correlation with transmembrane voltage, and continuum models of electropermeabilization that disregard the molecular-level structure and events. We then present insights from molecular-level modeling, particularly atomistic simulations that enhance understanding of pore formation, and evidence of chemical modifications of membrane lipids and functional modulation of membrane proteins affecting membrane permeability. Finally, we discuss the remaining challenges to our full understanding of electroporation and electropermeabilization.
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