Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
 
ID 3893687
Author(s) Perez, Camilo; Koshy, Caroline; Yildiz, Ozkan; Ziegler, Christine
Author(s) at UniBasel Perez, Camilo
Year 2012
Title Alternating-access mechanism in conformationally asymmetric trimers of the betaine transporter BetP
Journal Nature
Volume 490
Number 7418
Pages / Article-Number 126-30
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.
Publisher Macmillan
ISSN/ISBN 0028-0836 ; 1476-4687
edoc-URL http://edoc.unibas.ch/56045/
Full Text on edoc No
Digital Object Identifier DOI 10.1038/nature11403
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/22940865
ISI-Number WOS:000309446800046
Document type (ISI) Journal Article
 
   

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