Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1
Joint Authors
Jones, Peter M.
Curmi, Paul M. G.
Valenzuela, Stella M.
George, Anthony M.
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-09-08
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
The chloride intracellular channel (CLIC) family of proteins has the remarkable property of maintaining both a soluble form and an integral membrane form acting as an ion channel.
The soluble form is structurally related to the glutathione-S-transferase family, and CLIC can covalently bind glutathione via an active site cysteine.
We report approximately 0.6 μs of molecular dynamics simulations, encompassing the three possible ligand-bound states of CLIC1, using the structure of GSH-bound human CLIC1.
Noncovalently bound GSH was rapidly released from the protein, whereas the covalently ligand-bound protein remained close to the starting structure over 0.25 μs of simulation.
In the unliganded state, conformational changes in the vicinity of the glutathione-binding site resulted in reduced reactivity of the active site thiol.
Elastic network analysis indicated that the changes in the unliganded state are intrinsic to the protein architecture and likely represent functional transitions.
Overall, our results are consistent with a model of CLIC function in which covalent binding of glutathione does not occur spontaneously but requires interaction with another protein to stabilise the GSH binding site and/or transfer of the ligand.
The results do not indicate how CLIC1 undergoes a radical conformational change to form a transmembrane chloride channel but further elucidate the mechanism by which CLICs are redox controlled.
American Psychological Association (APA)
Jones, Peter M.& Curmi, Paul M. G.& Valenzuela, Stella M.& George, Anthony M.. 2013. Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1. BioMed Research International،Vol. 2013, no. 2013, pp.1-14.
https://search.emarefa.net/detail/BIM-1003603
Modern Language Association (MLA)
Jones, Peter M.…[et al.]. Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1. BioMed Research International No. 2013 (2013), pp.1-14.
https://search.emarefa.net/detail/BIM-1003603
American Medical Association (AMA)
Jones, Peter M.& Curmi, Paul M. G.& Valenzuela, Stella M.& George, Anthony M.. Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-14.
https://search.emarefa.net/detail/BIM-1003603
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1003603