Structure and mechanism of an active lipid-linked oligosaccharide flippase

Perez, Camilo; Gerber, Sabina; Boilevin, Jérémy; Bucher, Monika; Darbre, Tamis; Aebi, Markus; Reymond, Jean-Louis; Locher, Kaspar P. (2015). Structure and mechanism of an active lipid-linked oligosaccharide flippase. Nature, 524(7566), pp. 433-438. Macmillan Journals Ltd. 10.1038/nature14953

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The flipping of membrane-embedded lipids containing large, polar head groups is slow and energetically unfavourable, and is therefore catalysed by flippases, the mechanisms of which are unknown. A prominent example of a flipping reaction is the translocation of lipid-linked oligosaccharides that serve as donors in N-linked protein glycosylation. In Campylobacter jejuni, this process is catalysed by the ABC transporter PglK. Here we present a mechanism of PglK-catalysed lipid-linked oligosaccharide flipping based on crystal structures in distinct states, a newly devised in vitro flipping assay, and in vivo studies. PglK can adopt inward- and outward-facing conformations in vitro, but only outward-facing states are required for flipping. While the pyrophosphate-oligosaccharide head group of lipid-linked oligosaccharides enters the translocation cavity and interacts with positively charged side chains, the lipidic polyprenyl tail binds and activates the transporter but remains exposed to the lipid bilayer during the reaction. The proposed mechanism is distinct from the classical alternating-access model applied to other transporters.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Departement of Chemistry and Biochemistry

UniBE Contributor:

Boilevin, Jérémy; Darbre, Tamis and Reymond, Jean-Louis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

ISSN:

0028-0836

Publisher:

Macmillan Journals Ltd.

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

22 Jan 2016 14:40

Last Modified:

26 Jun 2016 02:09

Publisher DOI:

10.1038/nature14953

BORIS DOI:

10.7892/boris.74716

URI:

https://boris.unibe.ch/id/eprint/74716

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