The VSV-E1-Q1 construct was co-expressed in HEK293 cells with either pcDNA3.1, SAR1-H79G or KCNQ1-E261D. Cells expressing VSV-E1-Q1 with pcDNA3.1 were incubated with either 10 μM wortmannin (WTM) for 1 hour or 5 μM brefeldin A (Brf A) for 24 hours before the start of the assay. Each condition was performed in triplicate.

2021年7月20日 · Using recent structures of KCNQ1 and KCNE beta subunits in different states, we present a mechanism by which KCNE1 rotates the VSD relative to the PD and affects the VSD–PD coupling of KCNQ1...

To better discriminate differences in cellular localization of KCNQ1 between S and AS subjects, we transfected the iPSC-CMs with a plasmid over-expressing wild-type (WT) or mutant KCNQ1 proteins fused with a VSV tag located on the extracellular N-terminal domain. 11 VSV-positive staining of WT KCNQ1 was present in S-, AS-, and CTR-iPSC-CMs but ...

2006年10月19日 · As illustrated in figure 4C, the WT VSV-tagged KCNE1-KCNQ1 fusion protein, but not the fusion-proteins containing Y111C, L114P and P117L mutations, was readily detected with extracellular anti-VSV antibody. These data demonstrate that the presence of KCNE1 is not sufficient to restore KCNQ1 trafficking to the cell surface.

2008年8月1日 · KCNQ1 (alias KvLQT1 or Kv7.1) and KCNE1 (alias IsK or minK) co-assemble to form the voltage-activated K + channel responsible for IKs —a major repolarizing current in the human heart—and their dysfunction promotes cardiac arrhythmias. The channel is a component of larger macromolecular complexes containing known and undefined regulatory proteins.

2020年2月25日 · KCNQ1 adopts the canonical structural organization of the K V superfamily in which the central homotetrameric pore domain is flanked by four VSDs, each with four transmembrane helical segments (S1-S4).

2020年1月23日 · KCNQ1, also known as Kv7.1, is a voltage-dependent K + channel that regulates gastric acid secretion, salt and glucose homeostasis, and heart rhythm. Its functional properties are regulated in a tissue-specific manner through co …

2020年5月1日 · KCNQ1 presents a unique functional feature when compared to other VGLs, where it can switch from the voltage dependent state to the constitutively active state. The voltage sensor domain (Q1-VSD) can lose its voltage dependence upon association with members of the KCNE family making it constitutively active [35].

2022年11月3日 · In this study, we determined high-resolution cryo-electron microscopy structures of full-length human KCNQ1 with two VSD-PD coupling enhancers — the membrane lipid PIP 2 (phosphatidylinositol 4,5-bisphosphate) and a small-molecule ML277.

2021年7月20日 · Using recent structures of KCNQ1 and KCNE beta subunits in different states, we present a mechanism by which KCNE1 rotates the VSD relative to the PD and affects the VSD-PD coupling of KCNQ1 channels in a non-canonical way, forcing KCNQ1/KCNE1 channels to open in the fully-activated VSD state.