User:Laura Fountain/Chloride Ion Channel: Difference between revisions
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== About this Structure == | == About this Structure == | ||
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>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/ | 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>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>PMID:#11551966</ref> | ||
While this exact mechanism isn't known, it has been shown that functionality of the channel doesn't change whether it goes through 'normal' membrane integration via vesicles, or whether it's inserted into the intracellular space and allowed to integrate itself.<ref>PMID:#11940526</ref> Littler et. al. propose that upon oxidation CLIC1 undergoes a reversible transition from a monomeric to a non-covalent dimeric state due to the formation of an intramolecular disulfide bond (<scene name='User:Laura_Fountain/Sandbox_1/Cys_visualization/1'>Cys-24-Cys-59</scene>). They have determined the crystal structure of this oxidized state and show that a major structural transition has occurred, exposing a large hydrophobic surface, which forms the dimer interface. The oxidized CLIC1 dimer maintains its ability to form chloride ion channels in artificial bilayers and vesicles, whereas a reducing environment prevents the formation of ion channels by CLIC1. Their mutational studies show that both Cys-24 and Cys-59 are required for channel activity.<ref>PMID:#14613939</ref> | While this exact mechanism isn't known, it has been shown that functionality of the channel doesn't change whether it goes through 'normal' membrane integration via vesicles, or whether it's inserted into the intracellular space and allowed to integrate itself.<ref>PMID:#11940526</ref> Littler et. al. propose that upon oxidation CLIC1 undergoes a reversible transition from a monomeric to a non-covalent dimeric state due to the formation of an intramolecular disulfide bond (<scene name='User:Laura_Fountain/Sandbox_1/Cys_visualization/1'>Cys-24-Cys-59</scene>). They have determined the crystal structure of this oxidized state and show that a major structural transition has occurred, exposing a large hydrophobic surface, which forms the dimer interface. The oxidized CLIC1 dimer maintains its ability to form chloride ion channels in artificial bilayers and vesicles, whereas a reducing environment prevents the formation of ion channels by CLIC1. Their mutational studies show that both Cys-24 and Cys-59 are required for channel activity.<ref>PMID:#14613939</ref> | ||
