Gueler, Guennur and Gaertner, Rebecca M. and Ziegler, Christine and Maentele, Werner (2016) Lipid-Protein Interactions in the Regulated Betaine Symporter BetP Probed by Infrared Spectroscopy. JOURNAL OF BIOLOGICAL CHEMISTRY, 291 (9). pp. 4295-4307. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
The Na+-coupled betaine symporter BetP senses changes in the membrane state and increasing levels of cytoplasmic K+ during hyperosmotic stress latter via its C-terminal domain and regulates transport activity according to both stimuli. This intriguing sensing and regulation behavior of BetP was intensively studied in the past. It was shown by several biochemical studies that activation and regulation depends crucially on the lipid composition of the surrounding membrane. In fact, BetP is active and regulated only when negatively charged lipids are present. Recent structural studies have revealed binding of phosphatidylglycerol lipids to functional important parts of BetP, suggesting a functional role of lipid interactions. However, a regulatory role of lipid interactions could only be speculated from the snapshot provided by the crystal structure. Here, we investigate the nature of lipid-protein interactions of BetP reconstituted in closely packed two-dimensional crystals of negatively charged lipids and probed at the molecular level with Fourier transform infrared (FTIR) spectroscopy. The FTIR data indicate that K+ binding weakens the interaction of BetP especially with the anionic lipid head groups. We suggest a regulation mechanism in which lipid-protein interactions, especially with the C-terminal domain and the functional important gating helices transmembrane helice 3 (TMH3) and TMH12, confine BetP to its down-regulated transport state. As BetP is also activated by changes in the physical state of the membrane, our results point toward a more general mechanism of how active transport can be modified by dynamic lipid-protein interactions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | C-TERMINAL DOMAIN; CORYNEBACTERIUM-GLUTAMICUM; TRANSPORTER BETP; CARRIER BETP; GLYCINE-BETAINE; CONFORMATIONAL-CHANGES; BIOLOGICAL-MEMBRANES; PHASE-TRANSITIONS; K+; SPECIFICITY; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Mar 2019 07:26 |
| Last Modified: | 12 Mar 2019 07:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2386 |
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