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NMR resonance assignments and secondary structure of a mutant form of the human KCNE1 channel accessory protein that exhibits KCNE3-like function

NMR resonance assignments and secondary structure of a mutant form of the human KCNE1 channel... KCNQ1 (Q1) is a voltage-gated potassium channel that is modulated by members of the KCNE family, the best-characterized being KCNE1 (E1) and KCNE3 (E3). The Q1/E1 complex generates a channel with delayed activation and increased conductance. This complex is expressed in cardiomyocytes where it provides the IKs current that is critical for the repolarization phase of the cardiac action potential. The Q1/E3 complex, on the other hand, is expressed in epithelial cells of the colon and stomach, where it serves as a constitutively active leak channel to help maintain water and ion homeostasis. Studies show the single transmembrane segments (TMS) present in both E1 and E3 are essential to their distinct functions. More specifically, residues FTL located near the middle of the E1 TMS are essential for the delayed activation of Q1, while the corresponding TVG sites in E3 are critical for constitutive activation of the channel. Swapping these three residues leads to the switching of the functional properties for both Q1/E1FTL→TVG and Q1/E3TVG→FTL complexes. This work details the backbone assignments and chemical shifts for the E1FTL→TVG mutant, as determined using a suite of 3D NMR experiments along with specific and inverse amino acid isotopic labeling. The completed assignments can be used, in conjunction with other NMR experiments, to generate a 3D structure of E1FTL→TVG. The results of TALOS-N analysis of the chemical shifts are reported here. The E1FTL→TVG structure will be compared to the already available E1 and E3 structures to determine the roles that their TMS triplet motifs play in each protein to dictate their distinct channel-modulatory functions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biomolecular NMR Assignments Springer Journals

NMR resonance assignments and secondary structure of a mutant form of the human KCNE1 channel accessory protein that exhibits KCNE3-like function

Law, Cheryl; Sanders, Charles
Biomolecular NMR Assignments , Volume 13 (1) – Jan 2, 2019
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References (18)

Publisher
Springer Journals
Copyright
Copyright © 2019 by Springer Nature B.V.
Subject
Physics; Biological and Medical Physics, Biophysics; Polymer Sciences; Biochemistry, general
ISSN
1874-2718
eISSN
1874-270X
DOI
10.1007/s12104-018-09867-6
Publisher site
See Article on Publisher Site

Abstract

KCNQ1 (Q1) is a voltage-gated potassium channel that is modulated by members of the KCNE family, the best-characterized being KCNE1 (E1) and KCNE3 (E3). The Q1/E1 complex generates a channel with delayed activation and increased conductance. This complex is expressed in cardiomyocytes where it provides the IKs current that is critical for the repolarization phase of the cardiac action potential. The Q1/E3 complex, on the other hand, is expressed in epithelial cells of the colon and stomach, where it serves as a constitutively active leak channel to help maintain water and ion homeostasis. Studies show the single transmembrane segments (TMS) present in both E1 and E3 are essential to their distinct functions. More specifically, residues FTL located near the middle of the E1 TMS are essential for the delayed activation of Q1, while the corresponding TVG sites in E3 are critical for constitutive activation of the channel. Swapping these three residues leads to the switching of the functional properties for both Q1/E1FTL→TVG and Q1/E3TVG→FTL complexes. This work details the backbone assignments and chemical shifts for the E1FTL→TVG mutant, as determined using a suite of 3D NMR experiments along with specific and inverse amino acid isotopic labeling. The completed assignments can be used, in conjunction with other NMR experiments, to generate a 3D structure of E1FTL→TVG. The results of TALOS-N analysis of the chemical shifts are reported here. The E1FTL→TVG structure will be compared to the already available E1 and E3 structures to determine the roles that their TMS triplet motifs play in each protein to dictate their distinct channel-modulatory functions.

Journal

Biomolecular NMR Assignments – Springer Journals

Published: Jan 2, 2019

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