Perez, Camilo and Koshy, Caroline and Yildiz, Oezkan and Ziegler, Christine (2012) Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP. NATURE, 490 (7418). pp. 126-130. ISSN 0028-0836,
Full text not available from this repository. (Request a copy)Abstract
Betaine and Na+ symport has been extensively studied in the osmotically regulated transporter BetP from Corynebacterium glutamicum, a member of the betaine/choline/carnitine transporter family, which shares the conserved LeuT-like fold of two inverted structural repeats(1). BetP adjusts its transport activity by sensing the cytoplasmic K+ concentration as a measure for hyperosmotic stress via the osmosensing carboxy-terminal domain(2,3). BetP needs to be in a trimeric state for communication between individual protomers through several intratrimeric interaction sites(4). Recently, crystal structures of inward-facing BetP trimers have contributed to our understanding of activity regulation on a molecular level(5,6). Here we report new crystal structures, which reveal two conformationally asymmetric BetP trimers(7), capturing among them three distinct transport states. We observe a total of four new conformations at once: an outward-open apo and an outward-occluded apo state, and two closed transition states-one in complex with betaine and one substrate-free. On the basis of these new structures, we identified local and global conformational changes in BetP that underlie the molecular transport mechanism, which partially resemble structural changes observed in other sodium-coupled LeuT-like fold transporters, but show differences we attribute to the osmolytic nature of betaine, the exclusive substrate specificity and the regulatory properties of BetP.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NA+/BETAINE SYMPORTER BETP; CORYNEBACTERIUM-GLUTAMICUM; CRYSTAL-STRUCTURE; MOLECULAR-BASIS; CARRIER BETP; OPEN STATES; K+; HOMOLOG; BINDING; SODIUM; |
| 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: | 05 May 2020 07:01 |
| Last Modified: | 05 May 2020 07:01 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17957 |
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