Xu, Yanyan. Molecular mechanics investigation of the transport mechanisms in the CIC-ec1 H+/CI⁻ exchanger and P-glycoprotein/Sav1866 ABC transporter. 2014, PhD Thesis, University of Basel, Faculty of Science.
Official URL: http://edoc.unibas.ch/diss/DissB_11038
In the investigation of P-glycoprotein/Sav1866 systems, unambiguous conformational changes in trans-membrane domains were demonstrated for the first time, which involve rotation of helices that potentially contributes to allocrites transport. Nucleotide-binding domains experience small changes in which the two domains never completely dissociate. Asymmetric nucleotide occupancy states were accompanied by an opening of the trans-membrane domain, while no cavity was seen in symmetric nucleotide occupancy states. Q-loop and X-loop were identified to be two essential motifs in the coupling between trans-membrane domains and nucleotide binding domains.
In ClC-ec1, an open intracellular gate was demonstrated for the first time and identified to be essential for ion permeation. It was further found that the interaction between Y445 and I402 at helix O, controlled by the conformation of helix O, is related to the opening of the intracellular gate. Furthermore, conformational changes of F357 were identified to be also essential for chloride ion permeation. Two conformations of F357 are correlated with inward facing and outward facing conformations of ClC-ec1, which constitute the alternating mechanism of chloride ion transport. The conformation of F357 is correlated to ion occupancy in the pore as well as the conformation of E148. The transport of ClC-ec1 was proposed to take a modified alternating mechanism, in which the protein transports chloride ions by alternating between the outward facing and inward facing conformations, while the binding of chloride ion in the pore triggers proton transport.
|Committee Members:||Bernèche, Simon and Seelig-Löffler, Anna|
|Faculties and Departments:||05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)|
|Bibsysno:||Link to catalogue|
|Number of Pages:||81 S.|
|Last Modified:||30 Jun 2016 10:56|
|Deposited On:||18 Nov 2014 14:24|
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