6v1x

Publication Abstract from PubMed

Voltage-gated potassium (Kv) 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(1-3), the general determinants of channel gating polarity remain poorly understood(4). Here we suggest a molecular mechanism for electromechanical coupling and gating polarity in non-domain-swapped Kv channels on the basis of the cryo-electron microscopy structure of KAT1, the hyperpolarization-activated Kv 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 A 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(5), and may represent an unexpected link between depolarization- and hyperpolarization-activated channels.

Electromechanical coupling in the hyperpolarization-activated K(+) channel KAT1.,Clark MD, Contreras GF, Shen R, Perozo E Nature. 2020 Jul;583(7814):145-149. doi: 10.1038/s41586-020-2335-4. Epub 2020 May, 27. PMID:32461693^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.