Oct 26, 2018

PS membrane asymmetry influences the folding and insertion of a transmembrane helix

BioRxiv : the Preprint Server for Biology
Haden L. ScottFrancisco N. Barrera


The plasma membrane (PM) contains an asymmetric distribution of lipids between the inner and outer leaflets of its bilayer. A lipid of special interest in eukaryotic cells is the negatively charged phosphatidylserine (PS). In healthy cells, PS is actively sequestered to the inner leaflet of the PM but can redistribute to the outer leaflet when the cell is damaged or at the onset of apoptosis. The influence of PS asymmetry and its loss on membrane protein structure and organization have not been widely addressed. Marginally hydrophobic membrane proteins contain acidic residues in their transmembrane sequence, which can enable topological transitions after membrane association. The pH low insertion peptide (pHLIP), which undergoes a topological reorientation and inserts into the membrane at acidic pH, as its name implies, is a useful and well-characterized model for studying these transitions. Although it is known that the inclusion of PS in symmetric vesicles affects the membrane insertion process of pHLIP by lowering the pH midpoint of insertion, it is unclear how PS asymmetry influences these topological transitions. Here, we studied pHLIPs topology using freely-floating asymmetric phosphatidylcholine (PC)/PS vesicles with PS ...Continue Reading

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Mentioned in this Paper

Molecular Helix
Annexin A5
Integral Membrane Proteins
Pancreatic Carcinoma
Helix (Snails)
Integral to Membrane

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Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis