6V1X
Cryo-EM Structure of the Hyperpolarization-Activated Potassium Channel KAT1: Tetramer
Summary for 6V1X
| Entry DOI | 10.2210/pdb6v1x/pdb |
| EMDB information | 21018 |
| Descriptor | Potassium channel KAT1, (2S)-1-(nonanoyloxy)-3-(phosphonooxy)propan-2-yl tetradecanoate, (3beta,5beta,14beta,17alpha)-cholestan-3-ol (3 entities in total) |
| Functional Keywords | membrane protein, voltage-gated ion channel, potassium channel, transport protein |
| Biological source | Arabidopsis thaliana (Mouse-ear cress) |
| Total number of polymer chains | 4 |
| Total formula weight | 242203.66 |
| Authors | Clark, M.D.,Contreras, G.F.,Shen, R.,Perozo, E. (deposition date: 2019-11-21, release date: 2020-06-03, Last modification date: 2024-03-06) |
| Primary citation | Clark, M.D.,Contreras, G.F.,Shen, R.,Perozo, E. Electromechanical coupling in the hyperpolarization-activated K + channel KAT1. Nature, 583:145-149, 2020 Cited by PubMed Abstract: Voltage-gated potassium (K) channels coordinate electrical signalling and control cell volume by gating in response to membrane depolarization or hyperpolarization. However, although voltage-sensing domains transduce transmembrane electric field changes by a common mechanism involving the outward or inward translocation of gating charges, the general determinants of channel gating polarity remain poorly understood. Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped K channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated K channel from Arabidopsis thaliana. KAT1 displays a depolarized voltage sensor, which interacts with a closed pore domain directly via two interfaces and indirectly via an intercalated phospholipid. Functional evaluation of KAT1 structure-guided mutants at the sensor-pore interfaces suggests a mechanism in which direct interaction between the sensor and the C-linker hairpin in the adjacent pore subunit is the primary determinant of gating polarity. We suggest that an inward motion of the S4 sensor helix of approximately 5-7 Å can underlie a direct-coupling mechanism, driving a conformational reorientation of the C-linker and ultimately opening the activation gate formed by the S6 intracellular bundle. This direct-coupling mechanism contrasts with allosteric mechanisms proposed for hyperpolarization-activated cyclic nucleotide-gated channels, and may represent an unexpected link between depolarization- and hyperpolarization-activated channels. PubMed: 32461693DOI: 10.1038/s41586-020-2335-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.5 Å) |
Structure validation
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