A mutation in the cardiac KV7.1 channel possibly disrupts interaction with Yotiao protein.
Biochem Biophys Res Commun
; 714: 149947, 2024 Jun 25.
Article
in En
| MEDLINE
| ID: mdl-38657442
ABSTRACT
Here, we characterized the p.Arg583His (R583H) Kv7.1 mutation, identified in two unrelated families suffered from LQT syndrome. This mutation is located in the HС-HD linker of the cytoplasmic portion of the Kv7.1 channel. This linker, together with HD helix are responsible for binding the A-kinase anchoring protein 9 (AKAP9), Yotiao. We studied the electrophysiological characteristics of the mutated channel expressed in CHO-K1 along with KCNE1 subunit and Yotiao protein, using the whole-cell patch-clamp technique. We found that R583H mutation, even at the heterozygous state, impedes IKs activation. Molecular modeling showed that HС and HD helixes of the C-terminal part of Kv7.1 channel are swapped along the C-terminus length of the channel and that R583 position is exposed to the outer surface of HC-HD tandem coiled-coil. Interestingly, the adenylate cyclase activator, forskolin had a smaller effect on the mutant channel comparing with the WT protein, suggesting that R583H mutation may disrupt the interaction of the channel with the adaptor protein Yotiao and, therefore, may impair phosphorylation of the KCNQ1 channel.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Long QT Syndrome
/
Cytoskeletal Proteins
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KCNQ1 Potassium Channel
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A Kinase Anchor Proteins
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2024
Type:
Article
Affiliation country:
China