1K0N,1RK4


Conserved Protein Domain Family
GST_N_CLIC

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cd03061: GST_N_CLIC 
Click on image for an interactive view with Cn3D
GST_N family, Chloride Intracellular Channel (CLIC) subfamily; composed of CLIC1-5, p64, parchorin and similar proteins. They are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division and apoptosis. They can exist in both water-soluble and membrane-bound states, and are found in various vesicles and membranes. Biochemical studies of the C. elegans homolog, EXC-4, show that the membrane localization domain is present in the N-terminal part of the protein. The structure of soluble human CLIC1 reveals that it is monomeric and it adopts a fold similar to GSTs, containing an N-terminal domain with a TRX fold and a C-terminal alpha helical domain. Upon oxidation, the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. The CLIC1 dimer bears no similarity to GST dimers. The redox-controlled structural rearrangement exposes a large hydrophobic surface, which is masked by dimerization in vitro. In vivo, this surface may represent the docking interface of CLIC1 in its membrane-bound state. The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity, however, in other subfamily members, the second cysteine is not conserved.
Statistics
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PSSM-Id: 239359
Aligned: 18 rows
Threshold Bit Score: 115.932
Created: 17-Feb-2005
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 5 residues -Click on image for an interactive view with Cn3D
Feature 1:GSH binding site [chemical binding site]
Evidence:
  • Structure:1KON; Human CLIC1 with bound GSH; contacts at 3.5A
  • Comment:Noncovalent bonding of GSH to CLIC 1 is weak in solution, but covalent complexes can be formed in different oxidizing conditions. The interactions between CLIC1 and GSH are different than those seen in GSH:GST complexes.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1               #           # #                                         #            #
1K0N_A      3 EEQPQVELFVKAGSDGAK-IGNCPFSQRLFMVLWLK----GVTFNVTTVDtkRRTETVQKLCPGGELPFLLYGTEVHTDT 77  human
1RK4_B      5 EEQPQVELFVKAGSDGAK-IGNCPFSQRLFMVLWLK----GVTFNVTTVDtkRRTETVQKLCPGGQLPFLLYGTEVHTDT 79  human
AAH73268    2 SEQPQVELFVKAANDGQS-IGNCPFSQRLFMVLWLK----GVTFNVTTVDmkKKPDILKDLAPGAQPPFLLFAGEVRTDT 76  African clawed frog
NP_997847   3 EEKPEVELFVKAGSDGQS-IGNCPFSQRLFMVLWLK----GVTFNVTTVDmkRKPEILKDLAPGAQPPFLLYGTEVKTDT 77  zebrafish
NP_572928  18 FDVPEIELIIKASTIDGRrKGACLFCQEYFMDLYLLaelkTISLKVTTVDmqKPPPDFRTNFEATHPPILIDNGLAILEN 97  fruit fly
XP_525107  12 KGCPTTEELQSQSRLTTMwLPPQCCCSRLFMILWLK----GVVFSVTIADlkRRPADLQNLPLRTHPPFITFNNEVKTNV 87  chimpanzee
AAH56036   11 ERDPDIELFVKAGSDGES-IGNCPFSQRLFMILWLK----GVVFNVTTVDlkRKPADLHNLAPGTHPPFLTFNGEVKTDV 85  African clawed frog
NP_998062 169 PNQPQVALFVKAGSDGES-IGNCPFSQRLFMILWLK----GVVFNVTTVDlkRKPADLHNLAPGTHPPFLTFNGEVKTDV 243 zebrafish
XP_420060 149 EEEYEIFMFVKAGIDGES-IGNCPFSQRLFMILWLK----GVVFNVTTVDlkRKPADLHNLAPGTHPPFLTFNGEVKTDV 223 chicken
CAI12764    1 MAETKLQLFVKASEDGES-VGHCPSCQRLFMVLLLK----GVPFTLTTVDtrRSPDVLKDFAPGSQLPILLYDSDAKTDT 75  human
Feature 1                     
1K0N_A     78 NKIEEFLEAVlCPPRY 93  human
1RK4_B     80 NKIEEFLEAVlCPPRY 95  human
AAH73268   77 NKIEEFLEETlCPPKY 92  African clawed frog
NP_997847  78 NKIEEFLEETlCPPKY 93  zebrafish
NP_572928  98 EKIERHIMKN-IPGGY 112 fruit fly
XP_525107  88 NKIEEFLEDIvCPPKY 103 chimpanzee
AAH56036   86 NKIEEFLEETlAPPRY 101 African clawed frog
NP_998062 244 NKIEEFLEEVlAPPKY 259 zebrafish
XP_420060 224 NKIEEFLEETlAPPKY 239 chicken
CAI12764   76 LQIEDFLEETlGPPDF 91  human

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