title: Structural evidence for functional lipid interactions in the betaine transporter BetP.
abstract: Bilayer lipids contribute to the stability of membrane transporters and are crucially involved in their proper functioning. However, the molecular knowledge of how surrounding lipids affect membrane transport is surprisingly limited and despite its general importance is rarely considered in the molecular description of a transport mechanism. One reason is that only few atomic resolution structures of channels or transporters reveal a functional interaction with lipids, which are difficult to detect in X-ray structures per se. Overcoming these difficulties, we report here on a new structure of the osmotic stress-regulated betaine transporter BetP in complex with anionic lipids. This lipid-associated BetP structure is important in the molecular understanding of osmoregulation due to the strong dependence of activity regulation in BetP on the presence of negatively charged lipids. We detected eight resolved palmitoyl-oleoyl phosphatidyl glycerol (PG) lipids mimicking parts of the membrane leaflets and interacting with key residues in transport and regulation. The lipid-protein interactions observed here in structural detail in BetP provide molecular insights into the role of lipids in osmoregulated secondary transport.
authors.affiliation: Department of Structural Biology, Max-Planck Institute of Biophysics, Frankfurt am Main, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Koshy
authors.forename: Eva S
authors.initials: ES
authors.lastname: Schweikhard
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Gärtner
authors.forename: Camilo
authors.initials: C
authors.lastname: Perez
authors.forename: Ozkan
authors.initials: O
authors.lastname: Yildiz
authors.forename: Christine
authors.initials: C
authors.lastname: Ziegler
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism*; D001622:Betaine / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D048230:Corynebacterium glutamicum / Q000201:enzymology*; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008958:Models, Molecular; D009997:Osmotic Pressure; D017434:Protein Structure, Tertiary; D027981:Symporters
chemical_list: D001426:Bacterial Proteins; C101652:BetP protein, Corynebacterium glutamicum; D002352:Carrier Proteins; D008055:Lipids; D027981:Symporters; D001622:Betaine