Noncanonical mechanism of voltage sensor coupling to pore revealed by tandem dimers of Shaker

• DOI: 10.1038/s41467-019-11545-7
• Publication Date: 2019-08-08T10:20:54Z
• Authors: João L. Carvalho-...; Francisco Bezanilla
• Keywords: Shaker; Tandem

In voltage-gated potassium channels (VGKC), voltage sensors (VSD) endow voltage-sensitivity to pore domains (PDs) through a not fully understood mechanism. Shaker-like VGKC show domain-swapped configuration: VSD of one subunit is covalently connected its PD by the protein backbone (far connection) and non-covalently next (near connection). VSD-to-PD coupling explained far connection only, therefore an additional mechanistic component may be based on near connection. Using tandem dimers Shaker we functional data distinguishing from connections. Near connections influence both voltage-dependence C-type inactivation at selectivity filter overall open probability. We speculate conserved residue in S5 (S412 Shaker), within van der Waals distance S4 residues key for noncanonical coupling. Natural mutations S412-homologous brain heart are related neurological cardiac diseases.