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• W3134764963 abstract "Significance Dysfunction of Na v 1.5, the primary cardiac Na v channel, is associated with multiple arrhythmia syndromes, exemplified by type 3 long QT syndrome (LQT3) and Brugada syndrome (BrS). Establishment of the structure-function relationship and mechanistic understanding of the disease variants will facilitate the development of antiarrhythmic drugs. Here we report the cryo-EM structure of human Na v 1.5-E1784K, the most common variant shared by LQT3 and BrS. Structural mapping of 91 LQT3-associated mutations reveal a hotspot that involves the fast inactivation segments. The high density of LQT3 mutation sites in this region can be reasonably interpreted by the “door wedge” model for fast inactivation, which was derived from our previous structural observations and is supported by a wealth of functional characterizations." @default.
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• W3134764963 date "2021-03-12" @default.
• W3134764963 modified "2023-10-16" @default.
• W3134764963 title "Structure of human Na _v 1.5 reveals the fast inactivation-related segments as a mutational hotspot for the long QT syndrome" @default.
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• W3134764963 doi "https://doi.org/10.1073/pnas.2100069118" @default.
• W3134764963 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7980460" @default.
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• W3134764963 hasPublicationYear "2021" @default.
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