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Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP

Perez, Camilo and Koshy, Caroline and Yildiz, Ozkan and Ziegler, Christine. (2012) Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP. Nature, 490 (7418). pp. 126-130.

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Official URL: http://edoc.unibas.ch/56045/

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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. BetP adjusts its transport activity by sensing the cytoplasmic K(+) concentration as a measure for hyperosmotic stress via the osmosensing carboxy-terminal domain. BetP needs to be in a trimeric state for communication between individual protomers through several intratrimeric interaction sites. Recently, crystal structures of inward-facing BetP trimers have contributed to our understanding of activity regulation on a molecular level. Here we report new crystal structures, which reveal two conformationally asymmetric BetP trimers, 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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics
UniBasel Contributors:Perez, Camilo
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Macmillan
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:30 Nov 2017 11:23
Deposited On:30 Nov 2017 11:23

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