8SDA
CryoEM structure of rat Kv2.1(1-598) L403A mutant in nanodiscs
Summary for 8SDA
| Entry DOI | 10.2210/pdb8sda/pdb |
| Related | 8SD3 |
| EMDB information | 40350 |
| Descriptor | Potassium voltage-gated channel subfamily B member 1, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, POTASSIUM ION (3 entities in total) |
| Functional Keywords | voltage-dependent potassium channel, membrane protein |
| Biological source | Rattus norvegicus (Norway rat) |
| Total number of polymer chains | 4 |
| Total formula weight | 285757.62 |
| Authors | Tan, X.,Swartz, K.J. (deposition date: 2023-04-06, release date: 2023-09-27, Last modification date: 2023-10-25) |
| Primary citation | Fernandez-Marino, A.I.,Tan, X.F.,Bae, C.,Huffer, K.,Jiang, J.,Swartz, K.J. Inactivation of the Kv2.1 channel through electromechanical coupling. Nature, 622:410-417, 2023 Cited by PubMed Abstract: The Kv2.1 voltage-activated potassium (Kv) channel is a prominent delayed-rectifier Kv channel in the mammalian central nervous system, where its mechanisms of activation and inactivation are critical for regulating intrinsic neuronal excitability. Here we present structures of the Kv2.1 channel in a lipid environment using cryo-electron microscopy to provide a framework for exploring its functional mechanisms and how mutations causing epileptic encephalopathies alter channel activity. By studying a series of disease-causing mutations, we identified one that illuminates a hydrophobic coupling nexus near the internal end of the pore that is critical for inactivation. Both functional and structural studies reveal that inactivation in Kv2.1 results from dynamic alterations in electromechanical coupling to reposition pore-lining S6 helices and close the internal pore. Consideration of these findings along with available structures for other Kv channels, as well as voltage-activated sodium and calcium channels, suggests that related mechanisms of inactivation are conserved in voltage-activated cation channels and likely to be engaged by widely used therapeutics to achieve state-dependent regulation of channel activity. PubMed: 37758949DOI: 10.1038/s41586-023-06582-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.32 Å) |
Structure validation
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