Light-independent phospholipid scramblase activity of bacteriorhodopsin from Halobacterium salinarum

Verchère, Alice; Ou, Wei-Lin; Ploier, Birgit; Morizumi, Takefumi; Goren, Michael A.; Bütikofer, Peter; Ernst, Oliver P.; Khelashvili, George; Menon, Anant K.

doi:10.1038/s41598-017-09835-5

Title: Light-independent phospholipid scramblase activity of bacteriorhodopsin from Halobacterium salinarum

Journal Article · Fri Aug 25 00:00:00 EDT 2017 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-017-09835-5· OSTI ID:1490733

Verchère, Alice ^[1]; Ou, Wei-Lin ^[2]; Ploier, Birgit ^[1]; Morizumi, Takefumi ^[2]; Goren, Michael A. ^[1]; Bütikofer, Peter ^[3];

^[4]; Khelashvili, George ^[5];

^[1]

Weill Cornell Medical College, New York, NY (United States). Dept. of Biochemistry
Univ. of Toronto, ON (Canada). Dept. of Biochemistry
Univ. of Bern (Switzerland). Inst. of Biochemistry and Molecular Medicine
Univ. of Toronto, ON (Canada). Dept. of Biochemistry and Dept. of Molecular Genetics
Weill Cornell Medical College, New York, NY (United States). Dept. of Physiology and Biophysics, and Inst. for Computational Biomedicine

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. Finally, these results suggest that the lipid translocation pathway may lie at or near the interface of the protomers of a BR trimer.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1490733

Journal Information:: Scientific Reports, Vol. 7, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 16 works

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