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Computational Analysis of the Soluble Form of the Intracellular Chloride Ion Channel Protein CLIC1
- Source :
- BioMed Research International, Vol 2013 (2013), BioMed Research International
- Publication Year :
- 2013
- Publisher :
- Hindawi Limited, 2013.
-
Abstract
- 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 s 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 s 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.
- Subjects :
- Conformational change
Article Subject
Protein Conformation
Medical Biotechnology
lcsh:Medicine
Ion Channel Protein
Crystallography, X-Ray
Ligands
General Biochemistry, Genetics and Molecular Biology
Protein structure
Chlorides
Chloride Channels
Catalytic Domain
Humans
Amino Acid Sequence
Cysteine
Binding site
Ion channel
Binding Sites
General Immunology and Microbiology
biology
Chemistry
Ligand
lcsh:R
Computational Biology
Active site
General Medicine
Glutathione
Biochemistry
Chloride channel
biology.protein
Biophysics
Research Article
Protein Binding
Subjects
Details
- ISSN :
- 23146141 and 23146133
- Volume :
- 2013
- Database :
- OpenAIRE
- Journal :
- BioMed Research International
- Accession number :
- edsair.doi.dedup.....a7601b3dd5e5c04f00fee0fb07d4b347
- Full Text :
- https://doi.org/10.1155/2013/170586