User:Laura Fountain/Chloride Ion Channel: Difference between revisions
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== CLIC1: A Chloride Ion Channel == | == CLIC1: A Chloride Ion Channel == | ||
The CLIC family consists of seven members: CLIC1-5, p64, and parchorin. CLIC1 is the most commonly studied member of the CLIC family because it is expressed to some extent in most tissues and cell types that have been studied and is particularly highly expressed in muscle.<ref name="Tulk">PMID:11940526</ref> CLIC1 has also been found in various intracellular membranes such as the mitochondrial, nuclear, and endoplasmic reticular membranes.<ref name="Transition">PMID:12202911</ref> | |||
CLIC1 is a member of the highly conserved class of chloride ion channels that exist in both soluble and integral membrane forms. When disrupted cells are washed approximately half of the CLIC1 proteins will remain within the fractioned membrane as would be expected from an integral membrane protein. Atypically, the other half will behave as a soluble cytoplasmic protein and exist within the aqueous extract.<ref name="Tulk">PMID:11940526</ref> | |||
This is part of the evidence which leads Tulk et. al. to postulate that CLIC1 is among the small group of proteins which are assembled as soluble cytoplasmic proteins, which will then insert themselves into the appropriate membrane via their own mechanism. | |||
== | == Structure == | ||
<applet load='1k0o' size='300' frame='true' align='right' caption='Soluble form of CLIC1' /> | <applet load='1k0o' size='300' frame='true' align='right' caption='Soluble form of CLIC1' /> | ||
The CLIC family is defined by a COOH-terminal core segment of ~230 amino acids that are highly conserved among the family members. CLIC1 only contains a few amino acids upstream of the conserved core.<ref name="Tulk">PMID:11940526</ref> PUT IN SCENE WITH CONSERVATION COLORS | |||
Purified CLIC1 can integrate into synthetic lipid bilayers forming a chloride channel with similar properties to those observed in vivo. The structure of the soluble form of CLIC1 has been determined at 1.4-A resolution, and is shown to the right. It's a homodimeric structure with one pore per subunit, creating a "double barreled" channel. At its binding site in the pore, chloride interacts with the ends of four helices that come from both sides of the membrane. A <scene name='User:Laura_Fountain/Sandbox_1/Glutamate_residue/1'>glutamate residue</scene> that protrudes into the pore is proposed to participate in gating.<ref name="CLC">PMID:12163078</ref> Integration of CLIC1 into the membrane is likely to require a major structural rearrangement, probably of the N-domain (<scene name='User:Laura_Fountain/Sandbox_1/N-domain/3'>residues 1-90</scene>), with the putative transmembrane helix arising from residues in the vicinity of the redox-active site.<ref name="Crystal">PMID:11551966</ref> | Purified CLIC1 can integrate into synthetic lipid bilayers forming a chloride channel with similar properties to those observed in vivo. The structure of the soluble form of CLIC1 has been determined at 1.4-A resolution, and is shown to the right. It's a homodimeric structure with one pore per subunit, creating a "double barreled" channel. At its binding site in the pore, chloride interacts with the ends of four helices that come from both sides of the membrane. A <scene name='User:Laura_Fountain/Sandbox_1/Glutamate_residue/1'>glutamate residue</scene> that protrudes into the pore is proposed to participate in gating.<ref name="CLC">PMID:12163078</ref> Integration of CLIC1 into the membrane is likely to require a major structural rearrangement, probably of the N-domain (<scene name='User:Laura_Fountain/Sandbox_1/N-domain/3'>residues 1-90</scene>), with the putative transmembrane helix arising from residues in the vicinity of the redox-active site.<ref name="Crystal">PMID:11551966</ref> | ||
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1K0O is a 2 chains structure of sequences from Homo sapiens. The protein is monomeric and structurally homologous to the glutathione S-transferase superfamily, and it has a redox-active site resembling glutaredoxin. The structure of the complex of CLIC1 with glutathione shows that glutathione occupies the redox-active site, which is adjacent to an open, elongated slot lined by basic residues. This structure indicates that CLIC1 is likely to be controlled by redox-dependent processes.<ref name="Crystal">PMID:11551966</ref> | 1K0O is a 2 chains structure of sequences from Homo sapiens. The protein is monomeric and structurally homologous to the glutathione S-transferase superfamily, and it has a redox-active site resembling glutaredoxin. The structure of the complex of CLIC1 with glutathione shows that glutathione occupies the redox-active site, which is adjacent to an open, elongated slot lined by basic residues. This structure indicates that CLIC1 is likely to be controlled by redox-dependent processes.<ref name="Crystal">PMID:11551966</ref> | ||
== Selectivity for Chloride == | |||
== Function Within Cell == | |||
Because when expressed in cultured cells, their chloride ion activity increases, the most likely function is as a chloride channel. | |||
== Potential Ion Gating == | |||
== References == | == References == | ||
<references/> | <references/> | ||
