Kv channel gating requires a compatible S4-S5 linker and bottom part of S6, constrained by non-interacting residues

Journal article

Voltage-dependent K⁺ channels transfer the voltage sensor movement into gate opening or closure through an electromechanical coupling. To test functionally whether an interaction between the S4-S5 linker (L45) and the cytoplasmic end of S6 (S6_T) constitutes this coupling, the L45 in hKv1.5 was replaced by corresponding hKv2.1 sequence. This exchange was not tolerated but could be rescued by also swapping (S6_T). Exchanging both L45 and (S6_T) residue substitution scan of L45 and (S6_T) in hKv1.5 further shows that (S6_T) needs to be α-helical and forms a "crevice" in which residues I422 and T426 of L45 reside. These residues transfer the mechanical energy onto the (S6_T) crevice, whereas other residues in (S6_T) and L45 that are not involved in the interaction maintain the correct structure of the coupling.

Authors: Labro, A; Raes, A; Grottesi, A; Van Hoorick, D; Sansom, M

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Rockefeller University Press
• Journal: Journal of General Physiology
• Volume: 132
• Issue: 6
• Pages: 667-680
• Publication date: 2008-12-01
• Edition: Publisher's version
• DOI: 10.1085/jgp.200810048
• EISSN: 1540-7748
• ISSN: 0022-1295
• Language: English
• Subjects: Biochemistry; Molecular biophysics (biochemistry)