Light-independent phospholipid scramblase activity of bacteriorhodopsin from Halobacterium salinarum
| Autor: | Alice Verchère, Birgit Ploier, George Khelashvili, Takefumi Morizumi, Oliver P. Ernst, Wei-Lin Ou, Michael A. Goren, Peter Bütikofer, Anant K. Menon |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Halobacterium salinarum Models Molecular Phospholipid scramblase Light Protein Conformation lcsh:Medicine 610 Medicine & health Protomer 01 natural sciences Article 03 medical and health sciences Structure-Activity Relationship 0103 physical sciences Lipid translocation Phospholipid Transfer Proteins lcsh:Science Phospholipids Multidisciplinary 010304 chemical physics biology Retinylidene protein Vesicle lcsh:R Bacteriorhodopsin biology.organism_classification Recombinant Proteins Transmembrane domain 030104 developmental biology Biochemistry Bacteriorhodopsins Biophysics biology.protein 570 Life sciences lcsh:Q lipids (amino acids peptides and proteins) |
| Zdroj: | Verchère, Alice; Ou, Wei-Lin; Ploier, Birgit; Morizumi, Takefumi; Goren, Michael A; Bütikofer, Peter; Ernst, Oliver P; Khelashvili, George; Menon, Anant K (2017). Light-independent phospholipid scramblase activity of bacteriorhodopsin from Halobacterium salinarum. Scientific Reports, 7(1), p. 9522. Nature Publishing Group 10.1038/s41598-017-09835-5 Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-10 (2017) |
| Popis: | The retinylidene protein bacteriorhodopsin (BR) is a heptahelical light-dependent proton pump found in the purple membrane of the archaeon Halobacterium salinarum. We now show that when reconstituted into large unilamellar vesicles, purified BR trimers exhibit light-independent lipid scramblase activity, thereby facilitating transbilayer exchange of phospholipids between the leaflets of the vesicle membrane at a rate >10,000 per trimer per second. This activity is comparable to that of recently described scramblases including bovine rhodopsin and fungal TMEM16 proteins. Specificity tests reveal that BR scrambles fluorescent analogues of common phospholipids but does not transport a glycosylated diphosphate isoprenoid lipid. In silico analyses suggest that membrane-exposed polar residues in transmembrane helices 1 and 2 of BR may provide the molecular basis for lipid translocation by coordinating the polar head-groups of transiting phospholipids. Consistent with this possibility, extensive coarse-grained molecular dynamics simulations of a BR trimer in an explicit phospholipid membrane revealed water penetration along transmembrane helix 1 with the cooperation of a polar residue (Y147 in transmembrane helix 5) in the adjacent protomer. These results suggest that the lipid translocation pathway may lie at or near the interface of the protomers of a BR trimer. |
| Databáze: | OpenAIRE |
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