Key resources table.

Reagent type (species) or resource	Designation	Source or reference	Identifiers	Additional information
Gene (human)	KCNQ1	HUGO Gene Nomenclature Committee (HGNC)	Gene ID: 3784; HGNC:6294
Gene (human)	KCNE1	HUGO Gene Nomenclature Committee (HGNC)	Gene ID: 3753; HGNC:6240
Gene (human)	KCNE3	HUGO Gene Nomenclature Committee (HGNC)	Gene ID: 10008; HGNC:6243
Strain, strain background (Escherichia coli)	CT19 transaminase deficient strain	Dr. David Waugh, US National Cancer Institute PMID: 8914274		Used for special isotopic labeling of the KCNQ1 VSD for use in NMR studies.
Strain, strain background (Escherichia coli)	Rosetta/ C43(DE3)	Sigma-Aldrich	Catalog number 70954	Used for uniform isotopic labeling of KCNQ1 and amino acid-specific labeling for NMR.
Recombinant DNA reagent	pET16b expression plasmid encoding tagged human KCNQ1- (100-249)	PMID: 24606221		Used to express the human KCNQ1 VSD for NMR structural studies
Biological sample (include species here)	Xenopus oocytes (Xenopus laevis, female)	This paper	RRID:XEP_Xla	Xenopus laevis purchased from Nasco, Fort Atkinson, WI
Recombinant DNA reagent	pcDNA3.1 encoding human KCNQ1 or KCNE1	This paper	RRID:Addgene_111452	For site-directed mutagenesis
Commercial assay or kit	mMessage T7 polymerase kit	Applied Biosystems-Thermo Fisher Scientific	AM1344
Chemical compound, drug	XE991	Millipore Sigma	CAS #: 122955-42-4
Chemical compound, drug	Chromanol 293B	Millipore Sigma	CAS #: 163163-23-3
Chemical compound, drug	Alexa Fluor488 C5 maleimide	Molecular Probes, Eugene, OR	Catalog #: A10254
Software	Topspin 3.2	Bruker (Scientific Instruments Company)	RRID:SCR_014227	NMR data collection and processing.
Software	MDD and qMDD interface	URL: mddnmr.spektrino.com/ PMID: 21161328		NMR data processing
Software	NMRFAM-SPARKY	PMID: 25505092 URL: https://nmrfam.wisc.edu/nmrfam-sparky-distribution/		NMR data analysis and resonance assignments.
Software	TALOS-N	PMID:25502373 URL: spin.niddk.nih.gov/bax/software/TALOS-N/		Determination of secondary structure from NMR chemical shift data.
Software	CHARMM-GUI	PMID: 25130509 URL: www.charmm-gui.org/		Preparation of starting structures of the KCNQ1 VSD in lipid bilayers for MD restrained MD simulations.
Software	XPLOR-NIH	PMID: 28766807 URL: https://nmr.cit.nih.gov/xplor-nih/		Structure calculations using NMR data restraints
Software	GPU-accelerated AMBER 16	URL: https://ambermd.org/ PMID: 16200636		Program for execution of MD simulations.
Software	Lipid 17 AMBER	PMID: 24803855 URL: https://ambermd.org/AmberModels.php		Force field used for MD simulations.
Software	CPPTRAJ	PMID: 26583988 URL:https://amber-md.github.io/		Analysis of MD trajectoriesfollowing simulations.
Software	PatchMaster	HEKA	RRID:SCR_000034	Electrophysiology data collection
Software	IGOR	Wavemetrics, Lake Oswego, OR	RRID:SCR_000325	Electrophysiology data analysis
Software	Clampfit	Axon Instruments, Sunnyvale, CA	RRID:SCR_011323	Electrophysiology data analysis
Software	Sigmaplot	SPSS, San Jose, CA	RRID:SCR_003210	Electrophysiology data analysis and visualization
Software	MATLAB	MathWorks, MA	RRID:SCR_001622	Electrophysiology data analysis
Sequence-based reagent	For site-directed mutagenesis	This paper	PCR primers	PCR primers seq for mutations made in this study (each mutation utilizedtwo primers: b and c). E170R-b:cacgtacCTGgtcccgaagaacaccac; E170R-c: cgggacCAGgtacgtggtccgcctc; R237E-b: gcatcTCcaggatctgcaggaag; R237E-c:cagatcctgGAgatgctacacgtcgac F167R-b: ccgtcccgCGgaacaccaccagcac; F167R-c: gtgttcCGcgggacggagtacg Q234E-b:ggatctCcaggaagcggatgccc; Q234E-c: catccgcttcctgGagatcctgaggatgcta H240E-b: cggtcgacCTCtagcatcctcaggatc H240E-c: gctaGAGgtcgaccgccaggg D202N-b: cgatgaggtTAatgatggaaatgggcttc D202N-c: ccatcatTAacctcatcgtggtcgtg F351A-b: ggcaGCGcccgagccaagaatcc F351A-c: gctcgggCGCtgccctgaaggtgcag C214A-b: cttggaTcccacCGCgaggaccacca C214A-c: cGCGgtgggAtccaaggggcaggtg G219C-b: cctgaCacttggaTcccacCGC G219C-c: ggAtccaagtGtcaggtgtttgccacg C331A-b: gacagagaaTGCggaggcgatggtcttc C331A-c: ctccGCAttctctgtctttgccatc