Chloride Intracellular Channel Protein 2: Difference between revisions
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[[Image:Nfig001.jpg|300px|left|thumb| Localization of the different structures of CLIC2]] | [[Image:Nfig001.jpg|300px|left|thumb| Localization of the different structures of CLIC2]] | ||
<applet load='2r5g' size='500' frame='true' align='right' caption='CLIC2 ([2r5g]) resolution 1.86 Å' scene='Chloride_Intracellular_Channel_Protein_2/Structintro/2'/> | <applet load='2r5g' size='500' frame='true' align='right' caption='CLIC2 ([[2r5g]]) resolution 1.86 Å' scene='Chloride_Intracellular_Channel_Protein_2/Structintro/2'/> | ||
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[[Image:0.jpg]] | [[Image:0.jpg]] | ||
''Two different forms of | ''Two different forms of CLIC2 which differ by 18 residues: form A (blue) and form B (grey). | ||
'' | '' | ||
<applet load='2r5g' size='500' frame='true' align='right' caption='CLIC2 ([ | <applet load='2r5g' size='500' frame='true' align='right' caption='CLIC2 ([[2r5g]]) resolution 1.86 Å' /> | ||
Contrary to each members of the CLICs family, CLIC 2 is a monomer, no matter if it is oxydated or reduiced. It is composed of 247 amino acids, has a weight of 28.4kDa and an isoelectric point at 5.44(crystal structure). The CLIC2 molecule is box shaped (60×60×35 Å) and consists of a four strand core and two helices on one side. Comparing sequence similarities, the core is supposed to adopt the canonical fold of the glutathione S-transferase (GST) superfamily. This has been confirmed by the crystal structure determination of human CLIC1 at 1.4 Å resolution. Then, by analyzing CLIC genes sequences, this protein appears to have two potential transmembrane domains that would correspond to helices α1 and α6 in the GST-like structure of the soluble form. Thanks to immunological, electrophysical and proteolysis studies, we can say that membrane form of CLIC proteins cross the lipid bilayer an odd number of times. | Contrary to each members of the CLICs family, CLIC 2 is a monomer, no matter if it is oxydated or reduiced. It is composed of 247 amino acids, has a weight of 28.4kDa and an isoelectric point at 5.44(crystal structure). The CLIC2 molecule is box shaped (60×60×35 Å) and consists of a four strand core and two helices on one side. Comparing sequence similarities, the core is supposed to adopt the canonical fold of the glutathione S-transferase (GST) superfamily. This has been confirmed by the crystal structure determination of human CLIC1 at 1.4 Å resolution. Then, by analyzing CLIC genes sequences, this protein appears to have two potential transmembrane domains that would correspond to helices α1 and α6 in the GST-like structure of the soluble form. Thanks to immunological, electrophysical and proteolysis studies, we can say that membrane form of CLIC proteins cross the lipid bilayer an odd number of times. | ||
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===Similarity to other CLIC structures=== | ===Similarity to other CLIC structures=== | ||
<applet load='1K0M' size='300' frame='true' align='right' caption='CLIC1 ([ | <applet load='1K0M' size='300' frame='true' align='right' caption='CLIC1 ([[1k0m]]) resolution 1.40Å (initial scene) | ||
CLIC4 ([ | CLIC4 ([[2ahe]]) resolution 1.80Å (residues 58-75)' /> | ||
An interesting thing to do is to compare CLIC2 to other CLIC proteins to understand why they are distinguished. | An interesting thing to do is to compare CLIC2 to other CLIC proteins to understand why they are distinguished. | ||
Conserved regions in the glutathione S-transferase (GST) superfamily members appear to have a functional role since CLIC1 can interact with GST thanks to these regions. However, CLIC2 lost most of residues of CLIC1 that interact with GST except Lys 19 (<scene name='Sandbox123/Lys13/1'>Lys 13</scene> in CLIC1) and Cys 30 ( <scene name='Sandbox123/Cys_24/2'>Cys 24</scene> in CLIC1). In CLIC1, Lys 13 interacts with a glycyl carboxylate on GSH and Cys 24 forms a mixed disulfide bridge with GSH. The intramolecular disulfide bridge between Cys 30 and Cys 33 in CLIC2 prevents form binding between CLIC2 and GST. As a conclusion, between CLIC1 and CLIC2, the first difference is the loss of the GST binding site in CLIC2. | Conserved regions in the glutathione S-transferase (GST) superfamily members appear to have a functional role since CLIC1 can interact with GST thanks to these regions. However, CLIC2 lost most of residues of CLIC1 that interact with GST except Lys 19 (<scene name='Sandbox123/Lys13/1'>Lys 13</scene> in CLIC1) and Cys 30 ( <scene name='Sandbox123/Cys_24/2'>Cys 24</scene> in CLIC1). In CLIC1, Lys 13 interacts with a glycyl carboxylate on GSH and Cys 24 forms a mixed disulfide bridge with GSH. The intramolecular disulfide bridge between Cys 30 and Cys 33 in CLIC2 prevents form binding between CLIC2 and GST. As a conclusion, between CLIC1 and CLIC2, the first difference is the loss of the GST binding site in CLIC2. | ||
