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Mutations in the SH1 helix alter the thermal properties of myosin II

The myosin II SH1 helix is a joint that links the converter subdomain to the rest of the myosin motor domain and possibly plays a key role in the arrangement of the converter/lever arm. Several point mutations within the SH1 helix in human myosin IIs have been shown to cause diseases. To reveal whet...

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Detalles Bibliográficos
Autores principales: Shibata, Kotomi, Koyama, Tsubasa, Inde, Shohei, Iwai, Sosuke, Chaen, Shigeru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society of Japan (BSJ) 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468464/
https://www.ncbi.nlm.nih.gov/pubmed/28630813
http://dx.doi.org/10.2142/biophysico.14.0_67
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author Shibata, Kotomi
Koyama, Tsubasa
Inde, Shohei
Iwai, Sosuke
Chaen, Shigeru
author_facet Shibata, Kotomi
Koyama, Tsubasa
Inde, Shohei
Iwai, Sosuke
Chaen, Shigeru
author_sort Shibata, Kotomi
collection PubMed
description The myosin II SH1 helix is a joint that links the converter subdomain to the rest of the myosin motor domain and possibly plays a key role in the arrangement of the converter/lever arm. Several point mutations within the SH1 helix in human myosin IIs have been shown to cause diseases. To reveal whether these SH1 helix mutations affect not only motile activities but also thermal properties of myosin II, here we introduced the E683K or R686C point mutation into the SH1 helix in Dictyostelium myosin II. Thermal inactivation as well as thermal aggregation rates of these mutant proteins demonstrated that these mutations decreased the thermal stability of myosin II. Temperature dependence of sliding velocities of actin filaments showed that these mutations also reduced the activation energy of a rate-limiting process involved in actin movement. Given that these mutations are likely to alter coupling between the subdomains, and thus their thermal fluctuations, we propose that the SH1 helix is a key structural element that determines the flexibility and thermal properties of the myosin motor. These characteristics of the SH1 helix may contribute to the pathogenesis of the human diseases caused by mutations within this structural element.
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spelling pubmed-54684642017-06-19 Mutations in the SH1 helix alter the thermal properties of myosin II Shibata, Kotomi Koyama, Tsubasa Inde, Shohei Iwai, Sosuke Chaen, Shigeru Biophys Physicobiol Regular Article The myosin II SH1 helix is a joint that links the converter subdomain to the rest of the myosin motor domain and possibly plays a key role in the arrangement of the converter/lever arm. Several point mutations within the SH1 helix in human myosin IIs have been shown to cause diseases. To reveal whether these SH1 helix mutations affect not only motile activities but also thermal properties of myosin II, here we introduced the E683K or R686C point mutation into the SH1 helix in Dictyostelium myosin II. Thermal inactivation as well as thermal aggregation rates of these mutant proteins demonstrated that these mutations decreased the thermal stability of myosin II. Temperature dependence of sliding velocities of actin filaments showed that these mutations also reduced the activation energy of a rate-limiting process involved in actin movement. Given that these mutations are likely to alter coupling between the subdomains, and thus their thermal fluctuations, we propose that the SH1 helix is a key structural element that determines the flexibility and thermal properties of the myosin motor. These characteristics of the SH1 helix may contribute to the pathogenesis of the human diseases caused by mutations within this structural element. The Biophysical Society of Japan (BSJ) 2017-05-31 /pmc/articles/PMC5468464/ /pubmed/28630813 http://dx.doi.org/10.2142/biophysico.14.0_67 Text en 2017 © The Biophysical Society of Japan
spellingShingle Regular Article
Shibata, Kotomi
Koyama, Tsubasa
Inde, Shohei
Iwai, Sosuke
Chaen, Shigeru
Mutations in the SH1 helix alter the thermal properties of myosin II
title Mutations in the SH1 helix alter the thermal properties of myosin II
title_full Mutations in the SH1 helix alter the thermal properties of myosin II
title_fullStr Mutations in the SH1 helix alter the thermal properties of myosin II
title_full_unstemmed Mutations in the SH1 helix alter the thermal properties of myosin II
title_short Mutations in the SH1 helix alter the thermal properties of myosin II
title_sort mutations in the sh1 helix alter the thermal properties of myosin ii
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5468464/
https://www.ncbi.nlm.nih.gov/pubmed/28630813
http://dx.doi.org/10.2142/biophysico.14.0_67
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