
Open access
Author
Timachi, M. Hadi
Hutter, Cedric A.J.
Hohl, Michael
Assafa, Tufa
Böhm, Simon
Mittal, Anshumali
Seeger, Markus A.
Bordignon, Enrica
Date
2017-01Type
- Journal Article
Citations
Cited 25 times in
Web of Science
Cited 29 times in
Scopus
ETH Bibliography
yes
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Abstract
ABC exporters pump substrates across the membrane by coupling ATP-driven movements of nucleotide binding domains (NBDs) to the transmembrane domains (TMDs), which switch between inward- and outward-facing (IF, OF) orientations. DEER measurements on the heterodimeric ABC exporter TM287/288 from Thermotoga maritima, which contains a non-canonical ATP binding site, revealed that in the presence of nucleotides the transporter exists in an IF/OF equilibrium. While ATP binding was sufficient to partially populate the OF state, nucleotide trapping in the pre- or post-hydrolytic state was required for a pronounced conformational shift. At physiologically high temperatures and in the absence of nucleotides, the NBDs disengage asymmetrically while the conformation of the TMDs remains unchanged. Nucleotide binding at the degenerate ATP site prevents complete NBD separation, a molecular feature differentiating heterodimeric from homodimeric ABC exporters. Our data suggest hydrolysis-independent closure of the NBD dimer, which is further stabilized as the consensus site nucleotide is committed to hydrolysis. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000128122Publication status
publishedJournal / series
eLifeVolume
Pages / Article No.
Publisher
eLife Sciences PublicationsMore
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Citations
Cited 25 times in
Web of Science
Cited 29 times in
Scopus
ETH Bibliography
yes
Altmetrics