Xu, Yanyan and Seelig, Anna and Bernèche, Simon. (2017) Unidirectional Transport Mechanism in an ATP Dependent Exporter. ACS Central Science, 3 (3). pp. 250-258.
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Official URL: http://edoc.unibas.ch/54769/
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Abstract
ATP-binding cassette (ABC) transporters use the energy of ATP binding and hydrolysis to move a large variety of compounds across biological membranes. P-glycoprotein, involved in multidrug resistance, is the most investigated eukaryotic family member. Although a large number of biochemical and structural approaches have provided important information, the conformational dynamics underlying the coupling between ATP binding/hydrolysis and allocrite transport remains elusive. To tackle this issue, we performed molecular dynamic simulations for different nucleotide occupancy states of Sav1866, a prokaryotic P-glycoprotein homologue. The simulations reveal an outward-closed conformation of the transmembrane domain that is stabilized by the binding of two ATP molecules. The hydrolysis of a single ATP leads the X-loop, a key motif of the ATP binding cassette, to interfere with the transmembrane domain and favor its outward-open conformation. Our findings provide a structural basis for the unidirectionality of transport in ABC exporters and suggest a ratio of one ATP hydrolyzed per transport cycle.
Faculties and Departments: | 05 Faculty of Science > Departement Biozentrum > Former Organization Units Biozentrum > Biophysical Chemistry (Seelig A) |
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UniBasel Contributors: | Seelig-Löffler, Anna |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
Publisher: | American Chemical Society |
ISSN: | 2374-7943 |
e-ISSN: | 2374-7951 |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Language: | English |
Identification Number: |
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edoc DOI: | |
Last Modified: | 28 Feb 2022 18:08 |
Deposited On: | 02 Oct 2017 12:40 |
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