Lipid Bilayer Composition Can Influence the Orientation of Proteorhodopsin in Artificial Membranes

Tunuguntla, Ramya; Bangar, Mangesh A.; Kim, Kyunghoon; Stroeve, Pieter; Ajo‐Franklin, Caroline M.; Noy, Aleksandr

doi:10.1016/j.bpj.2013.07.043

Cited by 62 publications

(76 citation statements)

References 34 publications

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“…The ζ-potential of POPC:POPG LUVs was as expected negative, being significantly altered by addition of either AMP and becoming less negative as the concentration of MSI-78(4−20) and MSI-78 increased ( Figure 2B). 33 An overall change from approximately −28 mV to nearly neutral potential values was achieved after the addition of both peptides ( Figure 2B). However, the variation of the ζ-potential values was even more evident in the case of MSI-78 for lower concentrations (below 20 μM) of peptide ( Figure 2B).…”

Section: Molecular Pharmaceuticsmentioning

confidence: 95%

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

et al. 2015

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Antimicrobial peptides are widely recognized as an excellent alternative to conventional antibiotics. MSI-78, a highly effective and broad spectrum AMP, is one of the most promising AMPs for clinical application. In this study, we have designed shorter derivatives of MSI-78 with the aim of improving selectivity while maintaining antimicrobial activity. Shorter 17-mer derivatives were created by truncating MSI-78 at the N-and/or C-termini, while spanning MSI-78 sequence. Despite the truncations made, we found a 17-mer peptide, MSI-78(4−20) (KFLKKAKKFGKAFVKIL), which was demonstrated to be as effective as MSI-78 against the Gram-positive Staphylococcus strains tested and the Gram-negative Pseudomonas aeruginosa. This shorter derivative is more selective toward bacterial cells as it was less toxic to erythrocytes than MSI-78, representing an improved version of the lead peptide. Biophysical studies support a mechanism of action for based on the disruption of the bacterial membrane permeability barrier, which in turn leads to loss of membrane integrity and ultimately to cell death. These features point to a mechanism of action similar to the one described for the lead peptide MSI-78.

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Section: Molecular Pharmaceuticsmentioning

confidence: 95%

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

et al. 2015

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“…The Charge Balance Rule was recently tested in vitro with a eubacterial proteorhodopsin [89]. This seven TMD membrane protein has an inherent asymmetric surface charge density across the membrane.…”

Section: The Charge Balance Rulementioning

confidence: 99%

Lipids and topological rules governing membrane protein assembly

Bogdanov¹,

Dowhan²,

Vitrac³

2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

121

126

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Membrane protein folding and topogenesis are tuned to a given lipid profile since lipids and proteins have co-evolved to follow a set of interdependent rules governing final protein topological organization. Transmembrane domain (TMD) topology is determined via a dynamic process in which topogenic signals in the nascent protein are recognized and interpreted initially by the translocon followed by a given lipid profile in accordance with the Positive Inside Rule. The net zero charged phospholipid phosphatidylethanolamine and other neutral lipids dampen the translocation potential of negatively charged residues in favor of the cytoplasmic retention potential of positively charged residues (Charge Balance Rule). This explains why positively charged residues are more potent topological signals than negatively charged residues. Dynamic changes in orientation of TMDs during or after membrane insertion are attributed to non-sequential cooperative and collective lipid–protein charge interactions as well as long-term interactions within a protein. The proportion of dual topological conformers of a membrane protein varies in a dose responsive manner with changes in the membrane lipid composition not only in vivo but also in vitro and therefore is determined by the membrane lipid composition. Switching between two opposite TMD topologies can occur in either direction in vivo and also in liposomes (designated as fliposomes) independent of any other cellular factors. Such lipid-dependent post-insertional reversibility of TMD orientation indicates a thermodynamically driven process that can occur at any time and in any cell membrane driven by changes in the lipid composition. This dynamic view of protein topological organization influenced by the lipid environment reveals previously unrecognized possibilities for cellular regulation and understanding of disease states resulting from mis-folded proteins. This article is part of a Special Issue entitled: Protein Trafficking & Secretion.

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“…The charge balance rule also provides a molecular basis for TMD orientation of proteins, such as the multi-drug transporter EmrE (13), and low-molecular-weight transporters (14) in E. coli, which coexist as stable dual topological conformers in the membrane. Although several recent reports (15)(16)(17) independently demonstrate that initial lipid composition of proteoliposomes determines steady-state TMD orientation, evidence for dynamic reorientation postassembly in vitro is limited (7).…”

Section: Significancementioning

confidence: 99%

Dynamic membrane protein topological switching upon changes in phospholipid environment

Vitrac

MacLean

Jayaraman

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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A fundamental objective in membrane biology is to understand and predict how a protein sequence folds and orients in a lipid bilayer. Establishing the principles governing membrane protein folding is central to understanding the molecular basis for membrane proteins that display multiple topologies, the intrinsic dynamic organization of membrane proteins, and membrane protein conformational disorders resulting in disease. We previously established that lactose permease of Escherichia coli displays a mixture of topological conformations and undergoes postassembly bidirectional changes in orientation within the lipid bilayer triggered by a change in membrane phosphatidylethanolamine content, both in vivo and in vitro. However, the physiological implications and mechanism of dynamic structural reorganization of membrane proteins due to changes in lipid environment are limited by the lack of approaches addressing the kinetic parameters of transmembrane protein flipping. In this study, real-time fluorescence spectroscopy was used to determine the rates of protein flipping in the lipid bilayer in both directions and transbilayer flipping of lipids triggered by a change in proteoliposome lipid composition. Our results provide, for the first time to our knowledge, a dynamic picture of these events and demonstrate that membrane protein topological rearrangements in response to lipid modulations occur rapidly following a threshold change in proteoliposome lipid composition. Protein flipping was not accompanied by extensive lipid-dependent unfolding of transmembrane domains. Establishment of lipid bilayer asymmetry was not required but may accelerate the rate of protein flipping. Membrane protein flipping was found to accelerate the rate of transbilayer flipping of lipids.T here is limited understanding of how lipid environment affects membrane protein folding during exit from the translocon and insertion into the lipid bilayer or how dynamic changes in lipid environment affect the structure and folding of membrane proteins. Membrane protein lipid environment can change rapidly through lateral movement within a membrane, during trafficking along the secretion pathway, and locally in response to stimuli. Lipid environment is a determinant of transmembrane domain (TMD) orientation for several secondary transporters of Escherichia coli at the time of initial protein folding, as well as after final folding in the cell membrane (1). We used lactose permease (LacY), the paradigm of secondary transporters throughout nature (2), from E. coli as a model membrane protein to study how lipid-protein interactions determine inherently dynamic protein organization and function. When assembled in cells lacking phosphatidylethanolamine (PE), the net neutral and major phospholipid of E. coli (3) (Fig. 1), LacY exhibits inversion of the N-terminal (NT) six-TMD α-helical bundle with respect to the plane of the membrane bilayer and the C-terminal (CT) five-TMD bundle (4); TMD VII becomes an extramembrane domain (EMD) exposed to the periplasm a...

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Lipid Bilayer Composition Can Influence the Orientation of Proteorhodopsin in Artificial Membranes

Cited by 62 publications

References 34 publications

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

A 17-mer Membrane-Active MSI-78 Derivative with Improved Selectivity toward Bacterial Cells

Lipids and topological rules governing membrane protein assembly

Dynamic membrane protein topological switching upon changes in phospholipid environment

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