Structure of the CLC-1 chloride channel from Homo sapiens
CLC channels mediate passive Cl− conduction, while CLC transporters mediate active Cl− transport coupled to H+ transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different function...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2018-05-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/36629 |
| _version_ | 1811235997498736640 |
|---|---|
| author | Eunyong Park Roderick MacKinnon |
| author_facet | Eunyong Park Roderick MacKinnon |
| author_sort | Eunyong Park |
| collection | DOAJ |
| description | CLC channels mediate passive Cl− conduction, while CLC transporters mediate active Cl− transport coupled to H+ transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its ‘glutamate gate’ residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl− conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl− at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl− affinity distinguish CLC channels and transporters. |
| first_indexed | 2024-04-12T12:01:44Z |
| format | Article |
| id | doaj.art-c1b53cc3118c4812bf13520e6ec7d65d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:01:44Z |
| publishDate | 2018-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-c1b53cc3118c4812bf13520e6ec7d65d2022-12-22T03:33:51ZengeLife Sciences Publications LtdeLife2050-084X2018-05-01710.7554/eLife.36629Structure of the CLC-1 chloride channel from Homo sapiensEunyong Park0https://orcid.org/0000-0003-2994-5174Roderick MacKinnon1https://orcid.org/0000-0001-7605-4679Laboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesLaboratory of Molecular Neurobiology and Biophysics, Howard Hughes Medical Institute, The Rockefeller University, New York, United StatesCLC channels mediate passive Cl− conduction, while CLC transporters mediate active Cl− transport coupled to H+ transport in the opposite direction. The distinction between CLC-0/1/2 channels and CLC transporters seems undetectable by amino acid sequence. To understand why they are different functionally we determined the structure of the human CLC-1 channel. Its ‘glutamate gate’ residue, known to mediate proton transfer in CLC transporters, adopts a location in the structure that appears to preclude it from its transport function. Furthermore, smaller side chains produce a wider pore near the intracellular surface, potentially reducing a kinetic barrier for Cl− conduction. When the corresponding residues are mutated in a transporter, it is converted to a channel. Finally, Cl− at key sites in the pore appear to interact with reduced affinity compared to transporters. Thus, subtle differences in glutamate gate conformation, internal pore diameter and Cl− affinity distinguish CLC channels and transporters.https://elifesciences.org/articles/36629chloride channelCLCcryoelectron microscopy |
| spellingShingle | Eunyong Park Roderick MacKinnon Structure of the CLC-1 chloride channel from Homo sapiens eLife chloride channel CLC cryoelectron microscopy |
| title | Structure of the CLC-1 chloride channel from Homo sapiens |
| title_full | Structure of the CLC-1 chloride channel from Homo sapiens |
| title_fullStr | Structure of the CLC-1 chloride channel from Homo sapiens |
| title_full_unstemmed | Structure of the CLC-1 chloride channel from Homo sapiens |
| title_short | Structure of the CLC-1 chloride channel from Homo sapiens |
| title_sort | structure of the clc 1 chloride channel from homo sapiens |
| topic | chloride channel CLC cryoelectron microscopy |
| url | https://elifesciences.org/articles/36629 |
| work_keys_str_mv | AT eunyongpark structureoftheclc1chloridechannelfromhomosapiens AT roderickmackinnon structureoftheclc1chloridechannelfromhomosapiens |