Matches in SemOpenAlex for { <https://semopenalex.org/work/W2157797346> ?p ?o ?g. }
Showing items 1 to 81 of
81
with 100 items per page.
- W2157797346 abstract "The pore-forming α1C subunit of the voltage-gated L-type calcium channel (CaV1.2) consists of four concatenated Repeats (I-IV), each contributing a voltage-sensing domain (VSD, transmembrane helices S1-S4) and a quarter of the central ion-conductive pore domain (S5-S6). In Timothy Syndrome (TS), a rare and severe multi-organ disorder, specific alterations in CaV1.2 voltage-dependent properties lead to autism, immunodeficiency, QT prolongation (LQT8) and lethal arrhythmias. The most frequent TS-causing mutation (G406R) is located at the intracellular flank of S6 in Repeat I and promotes Ca2+ influx by (1) shifting CaV1.2 voltage- dependent activation towards more negative potentials and (2) impairing voltage-dependent inactivation. To gain insight on the molecular basis underlying the TS-causing voltage-sensitivity anomalies, we studied the structural rearrangements of VSDs I and III in human CaV1.2 channels carrying the G406R mutation, using the voltage-clamp fluorometry technique. Briefly, this involves conjugating a small, environment-sensitive fluorophore at a specific VSD that reports local conformational rearrangements as fluorescence changes. Under voltage-clamp, we simultaneously acquired ionic current and fluorescence signals, which corresponded to specific VSD rearrangements during channel activation. We found that the G406R mutation dramatically altered the operation of VSDs I and III compared to wild-type channels, by inducing a hyperpolarizing shift in their activation voltage dependence of ∼80mV and ∼50mV, respectively. These shifts were associated with a significant reduction in the effective valences of VSD I and III by ∼50% and ∼42%, respectively. Moreover, the sign of the fluorescence signals detected from TS channels was opposite to that observed in wild-type CaV1.2 channels. Taken together, these results suggest that the TS-causing mutation causes an overall structural perturbation, manifested as a change in both the fluorophore quenching process reported from VSD I and VSD III and their altered voltage-dependence. Funded by: NIH,AHA,FONDECYT,ACT." @default.
- W2157797346 created "2016-06-24" @default.
- W2157797346 creator A5024607908 @default.
- W2157797346 creator A5039769502 @default.
- W2157797346 creator A5048461375 @default.
- W2157797346 creator A5072174169 @default.
- W2157797346 creator A5075963331 @default.
- W2157797346 date "2014-01-01" @default.
- W2157797346 modified "2023-09-28" @default.
- W2157797346 title "A Timothy Syndrome Causing Mutation Perturbs Voltage Sensor Operation in Human CaV1.2 Channels" @default.
- W2157797346 doi "https://doi.org/10.1016/j.bpj.2013.11.1898" @default.
- W2157797346 hasPublicationYear "2014" @default.
- W2157797346 type Work @default.
- W2157797346 sameAs 2157797346 @default.
- W2157797346 citedByCount "0" @default.
- W2157797346 crossrefType "journal-article" @default.
- W2157797346 hasAuthorship W2157797346A5024607908 @default.
- W2157797346 hasAuthorship W2157797346A5039769502 @default.
- W2157797346 hasAuthorship W2157797346A5048461375 @default.
- W2157797346 hasAuthorship W2157797346A5072174169 @default.
- W2157797346 hasAuthorship W2157797346A5075963331 @default.
- W2157797346 hasBestOaLocation W21577973461 @default.
- W2157797346 hasConcept C100837961 @default.
- W2157797346 hasConcept C104292427 @default.
- W2157797346 hasConcept C104317684 @default.
- W2157797346 hasConcept C12554922 @default.
- W2157797346 hasConcept C170493617 @default.
- W2157797346 hasConcept C178790620 @default.
- W2157797346 hasConcept C181911157 @default.
- W2157797346 hasConcept C185592680 @default.
- W2157797346 hasConcept C18699975 @default.
- W2157797346 hasConcept C194544171 @default.
- W2157797346 hasConcept C2776972302 @default.
- W2157797346 hasConcept C501734568 @default.
- W2157797346 hasConcept C50254741 @default.
- W2157797346 hasConcept C519063684 @default.
- W2157797346 hasConcept C55493867 @default.
- W2157797346 hasConcept C86803240 @default.
- W2157797346 hasConceptScore W2157797346C100837961 @default.
- W2157797346 hasConceptScore W2157797346C104292427 @default.
- W2157797346 hasConceptScore W2157797346C104317684 @default.
- W2157797346 hasConceptScore W2157797346C12554922 @default.
- W2157797346 hasConceptScore W2157797346C170493617 @default.
- W2157797346 hasConceptScore W2157797346C178790620 @default.
- W2157797346 hasConceptScore W2157797346C181911157 @default.
- W2157797346 hasConceptScore W2157797346C185592680 @default.
- W2157797346 hasConceptScore W2157797346C18699975 @default.
- W2157797346 hasConceptScore W2157797346C194544171 @default.
- W2157797346 hasConceptScore W2157797346C2776972302 @default.
- W2157797346 hasConceptScore W2157797346C501734568 @default.
- W2157797346 hasConceptScore W2157797346C50254741 @default.
- W2157797346 hasConceptScore W2157797346C519063684 @default.
- W2157797346 hasConceptScore W2157797346C55493867 @default.
- W2157797346 hasConceptScore W2157797346C86803240 @default.
- W2157797346 hasLocation W21577973461 @default.
- W2157797346 hasOpenAccess W2157797346 @default.
- W2157797346 hasPrimaryLocation W21577973461 @default.
- W2157797346 hasRelatedWork W1971472046 @default.
- W2157797346 hasRelatedWork W1995461981 @default.
- W2157797346 hasRelatedWork W2026464229 @default.
- W2157797346 hasRelatedWork W2031935334 @default.
- W2157797346 hasRelatedWork W2045376687 @default.
- W2157797346 hasRelatedWork W2053726766 @default.
- W2157797346 hasRelatedWork W2061670240 @default.
- W2157797346 hasRelatedWork W2062148459 @default.
- W2157797346 hasRelatedWork W2316183102 @default.
- W2157797346 hasRelatedWork W2329775541 @default.
- W2157797346 hasRelatedWork W2330026356 @default.
- W2157797346 hasRelatedWork W2396266211 @default.
- W2157797346 hasRelatedWork W2506532786 @default.
- W2157797346 hasRelatedWork W2545550117 @default.
- W2157797346 hasRelatedWork W2789138156 @default.
- W2157797346 hasRelatedWork W2926832831 @default.
- W2157797346 hasRelatedWork W3003317613 @default.
- W2157797346 hasRelatedWork W3197400812 @default.
- W2157797346 hasRelatedWork W3197455755 @default.
- W2157797346 hasRelatedWork W3206313293 @default.
- W2157797346 isParatext "false" @default.
- W2157797346 isRetracted "false" @default.
- W2157797346 magId "2157797346" @default.
- W2157797346 workType "article" @default.