Abstract
Attachment of lipophilic groups is an important post‐translational modification of proteins, which involves the coupling of one or more anchors such as fatty acids, isoprenoids, phospholipids, or glycosylphosphatidyl inositols. To study its impact on the membrane partitioning of hydrophobic peptides or proteins, we designed a tyrosine‐based trifunctional linker. The linker allows the facile incorporation of two different functionalities at a cysteine residue in a single step. We determined the effect of the lipid modification on the membrane partitioning of the synthetic α‐helical model peptide WALP with or without here and in all cases below; palmitoyl groups in giant unilamellar vesicles that contain a liquid‐ordered (Lo) and liquid‐disordered (Ld) phase. Introduction of two palmitoyl groups did not alter the localization of the membrane peptides, nor did the membrane thickness or lipid composition. In all cases, the peptide was retained in the Ld phase. These data demonstrate that the Lo domain in model membranes is highly unfavorable for a single membrane‐spanning peptide.
Highlights
The traffic of proteins to the proper localization in the cell is necessary for their function
For the trifunctional linker designed here, a maleimide was introduced on O-propargyltyrosine, followed by an amide coupling with phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) to mimic two palmitoyl moieties
We report the synthesis and use of a trifunctional linker to study the localization of membrane proteins and peptides in phase-separating giant unilamellar vesicles (GUVs)
Summary
The traffic of proteins to the proper localization in the cell is necessary for their function. In many instances signal sequences determine the destination of a protein, be it the insertion within a membrane or translocation into the lumen of a compartment of a cell.[1,2,3] Remarkably, changes of a single amino acid residue can change the localization of lipoproteins from the inner to the outer membrane of Escherichia coli and vice versa.[4] reaching the correct compartment or target membrane is not necessarily enough for proper functioning of the protein. Biological membranes are heterogeneous in structure and localization within a specific membrane domain has been shown to affect the function of for example, Lymphocyte function-associated antigen 1 and Toll-like receptor 2, which are moved to more ordered domains upon bind-.
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