Sandboxjg
From Proteopedia
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<Structure load='1rd8' size='500' frame='true' align='right' caption='ClC Transporter' scene='Insert optional scene name here' /> | <Structure load='1rd8' size='500' frame='true' align='right' caption='ClC Transporter' scene='Insert optional scene name here' /> | ||
| - | The <scene name='Sandboxjg/1ots/2'>CLC-ec1 (1OTS) protein</scene> is a | + | The <scene name='Sandboxjg/1ots/2'>CLC-ec1 (1OTS) protein</scene> is a membrane protein of Escherichia coli which belongs to the CLC family of ion channels and transporters. These proteins are essential for the maintenance of proper membrane potential in muscle cells, for the transport of electrolytes across epithelial layers, and to regulate cell volume. |
| + | Roderick MacKinnon and his team determined the structure of this protein and proposed that it was a Cl- selective ion channel. Accardi and Miller showed that CLC-ec1 functions as a transporter: it exchanges 2 Cl- :1 H+ . | ||
| - | + | The CLC-ec1 transporter is a dimer formed of two polypeptide chains each containing an internal repeat arranged in an anti-parallel organization. Each monomer functions independently of the other and creates a passage for ions through the membrane. Its structure allows it to use electrostatic interactions with the dipoles of the α-helices and with nitrogen atoms and carboxyl groups in order to filter Cl- and H+ ions. Because each polypeptide chain functions independently, we will focus on the structure of one pore. | |
| - | + | There are 3 chloride binding sites in each monomer, an exterior binding site, a central binding site, and an interior binding site. These three sites span the membrane and define the transport pathway for Cl-. In the structure of the WT protein Glu 148 occupies either the central or the exterior binding sites where it likely competes with Cl- ions. Upon protonation the side chain of E148 extends towards the extracellular solution and opens the pathway allowing ion transport to occur. The H+ transport pathway in each monomer has two essential glutamate residues: one <scene name='Sandboxjg/Glu_148/1’>(Glu 148)</scene> functions as the coupling element between Cl- and H+ while the other <scene name='Sandboxjg/Glu_203/1’>(Glu 203)</scene>is involved in H+ permeation. | |
| - | + | One of the interesting properties of this protein family is that its members can function either as ion channels or transporters. Furthermore, mutating Glu 148 to Ala in CLC-ec1 eliminates H+ transport but chloride ions can still move freely through the protein giving rise to a channel-like behavior. Mutations in other family members cause myotonia congenital (CLC-1), osteopetrosis (CLC-7) and kidney pathologies such as Bartter’s syndrome (CLC-Ka and -Kb) and Dent’s disease (CLC-5). | |
| - | One of the interesting properties of this protein is that it can function as either a channel or a transporter. For instance, with certain mutations concerning the Glu 148,hydrogen ion activity is impaired, but chloride ions can still move freely through the protein. Other mutations can have the potential to cause diseases like cystic fibrosis, myotonia congenita, epilepsy, and others. | ||
To see the test <scene name='Sandboxjg/Test1ots/1'>click on me</scene> | To see the test <scene name='Sandboxjg/Test1ots/1'>click on me</scene> | ||
Revision as of 00:18, 23 September 2011
ClC Transporter
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The is a membrane protein of Escherichia coli which belongs to the CLC family of ion channels and transporters. These proteins are essential for the maintenance of proper membrane potential in muscle cells, for the transport of electrolytes across epithelial layers, and to regulate cell volume. Roderick MacKinnon and his team determined the structure of this protein and proposed that it was a Cl- selective ion channel. Accardi and Miller showed that CLC-ec1 functions as a transporter: it exchanges 2 Cl- :1 H+ .
The CLC-ec1 transporter is a dimer formed of two polypeptide chains each containing an internal repeat arranged in an anti-parallel organization. Each monomer functions independently of the other and creates a passage for ions through the membrane. Its structure allows it to use electrostatic interactions with the dipoles of the α-helices and with nitrogen atoms and carboxyl groups in order to filter Cl- and H+ ions. Because each polypeptide chain functions independently, we will focus on the structure of one pore.
There are 3 chloride binding sites in each monomer, an exterior binding site, a central binding site, and an interior binding site. These three sites span the membrane and define the transport pathway for Cl-. In the structure of the WT protein Glu 148 occupies either the central or the exterior binding sites where it likely competes with Cl- ions. Upon protonation the side chain of E148 extends towards the extracellular solution and opens the pathway allowing ion transport to occur. The H+ transport pathway in each monomer has two essential glutamate residues: one functions as the coupling element between Cl- and H+ while the other is involved in H+ permeation.
One of the interesting properties of this protein family is that its members can function either as ion channels or transporters. Furthermore, mutating Glu 148 to Ala in CLC-ec1 eliminates H+ transport but chloride ions can still move freely through the protein giving rise to a channel-like behavior. Mutations in other family members cause myotonia congenital (CLC-1), osteopetrosis (CLC-7) and kidney pathologies such as Bartter’s syndrome (CLC-Ka and -Kb) and Dent’s disease (CLC-5).
To see the test
