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A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin

Excitation-contraction coupling in skeletal muscle depends, in part, on a functional interaction between the ligand-gated ryanodine receptor (RyR1) and integral membrane protein Trisk 95, localized to the sarcoplasmic reticulum membrane. Various domains on Trisk 95 can associate with RyR1, yet the d...

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Detalles Bibliográficos
Autores principales: Wium, Elize, Dulhunty, Angela F., Beard, Nicole A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427183/
https://www.ncbi.nlm.nih.gov/pubmed/22937102
http://dx.doi.org/10.1371/journal.pone.0043817
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author Wium, Elize
Dulhunty, Angela F.
Beard, Nicole A.
author_facet Wium, Elize
Dulhunty, Angela F.
Beard, Nicole A.
author_sort Wium, Elize
collection PubMed
description Excitation-contraction coupling in skeletal muscle depends, in part, on a functional interaction between the ligand-gated ryanodine receptor (RyR1) and integral membrane protein Trisk 95, localized to the sarcoplasmic reticulum membrane. Various domains on Trisk 95 can associate with RyR1, yet the domain responsible for regulating RyR1 activity has remained elusive. We explored the hypothesis that a luminal Trisk 95 KEKE motif (residues 200–232), known to promote RyR1 binding, may also form the RyR1 activation domain. Peptides corresponding to Trisk 95 residues 200–232 or 200–231 bound to RyR1 and increased the single channel activity of RyR1 by 1.49±0.11-fold and 1.8±0.15-fold respectively, when added to its luminal side. A similar increase in [(3)H]ryanodine binding, which reflects open probability of the channels, was also observed. This RyR1 activation is similar to activation induced by full length Trisk 95. Circular dichroism showed that both peptides were intrinsically disordered, suggesting a defined secondary structure is not necessary to mediate RyR1 activation. These data for the first time demonstrate that Trisk 95′s 200–231 region is responsible for RyR1 activation. Furthermore, it shows that no secondary structure is required to achieve this activation, the Trisk 95 residues themselves are critical for the Trisk 95-RyR1 interaction.
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spelling pubmed-34271832012-08-30 A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin Wium, Elize Dulhunty, Angela F. Beard, Nicole A. PLoS One Research Article Excitation-contraction coupling in skeletal muscle depends, in part, on a functional interaction between the ligand-gated ryanodine receptor (RyR1) and integral membrane protein Trisk 95, localized to the sarcoplasmic reticulum membrane. Various domains on Trisk 95 can associate with RyR1, yet the domain responsible for regulating RyR1 activity has remained elusive. We explored the hypothesis that a luminal Trisk 95 KEKE motif (residues 200–232), known to promote RyR1 binding, may also form the RyR1 activation domain. Peptides corresponding to Trisk 95 residues 200–232 or 200–231 bound to RyR1 and increased the single channel activity of RyR1 by 1.49±0.11-fold and 1.8±0.15-fold respectively, when added to its luminal side. A similar increase in [(3)H]ryanodine binding, which reflects open probability of the channels, was also observed. This RyR1 activation is similar to activation induced by full length Trisk 95. Circular dichroism showed that both peptides were intrinsically disordered, suggesting a defined secondary structure is not necessary to mediate RyR1 activation. These data for the first time demonstrate that Trisk 95′s 200–231 region is responsible for RyR1 activation. Furthermore, it shows that no secondary structure is required to achieve this activation, the Trisk 95 residues themselves are critical for the Trisk 95-RyR1 interaction. Public Library of Science 2012-08-24 /pmc/articles/PMC3427183/ /pubmed/22937102 http://dx.doi.org/10.1371/journal.pone.0043817 Text en © 2012 Wium et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Wium, Elize
Dulhunty, Angela F.
Beard, Nicole A.
A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin
title A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin
title_full A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin
title_fullStr A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin
title_full_unstemmed A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin
title_short A Skeletal Muscle Ryanodine Receptor Interaction Domain in Triadin
title_sort skeletal muscle ryanodine receptor interaction domain in triadin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427183/
https://www.ncbi.nlm.nih.gov/pubmed/22937102
http://dx.doi.org/10.1371/journal.pone.0043817
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