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Conformational spread drives the evolution of the calcium–calmodulin protein kinase II
The calcium calmodulin (Ca(2+)/CaM) dependent protein kinase II (CaMKII) decodes Ca(2+) frequency oscillations. The CaMKIIα isoform is predominantly expressed in the brain and has a central role in learning. I matched residue and organismal evolution with collective motions deduced from the atomic s...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120016/ https://www.ncbi.nlm.nih.gov/pubmed/35589775 http://dx.doi.org/10.1038/s41598-022-12090-y |
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author | Khan, Shahid |
author_facet | Khan, Shahid |
author_sort | Khan, Shahid |
collection | PubMed |
description | The calcium calmodulin (Ca(2+)/CaM) dependent protein kinase II (CaMKII) decodes Ca(2+) frequency oscillations. The CaMKIIα isoform is predominantly expressed in the brain and has a central role in learning. I matched residue and organismal evolution with collective motions deduced from the atomic structure of the human CaMKIIα holoenzyme to learn how its ring architecture abets function. Protein dynamic simulations showed its peripheral kinase domains (KDs) are conformationally coupled via lateral spread along the central hub. The underlying β-sheet motions in the hub or association domain (AD) were deconvolved into dynamic couplings based on mutual information. They mapped onto a coevolved residue network to partition the AD into two distinct sectors. A second, energetically stressed sector was added to ancient bacterial enzyme dimers for assembly of the ringed hub. The continued evolution of the holoenzyme after AD–KD fusion targeted the sector’s ring contacts coupled to the KD. Among isoforms, the α isoform emerged last and, it alone, mutated rapidly after the poikilotherm–homeotherm jump to match the evolution of memory. The correlation between dynamics and evolution of the CaMKII AD argues single residue substitutions fine-tune hub conformational spread. The fine-tuning could increase CaMKIIα Ca(2+) frequency response range for complex learning functions. |
format | Online Article Text |
id | pubmed-9120016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91200162022-05-21 Conformational spread drives the evolution of the calcium–calmodulin protein kinase II Khan, Shahid Sci Rep Article The calcium calmodulin (Ca(2+)/CaM) dependent protein kinase II (CaMKII) decodes Ca(2+) frequency oscillations. The CaMKIIα isoform is predominantly expressed in the brain and has a central role in learning. I matched residue and organismal evolution with collective motions deduced from the atomic structure of the human CaMKIIα holoenzyme to learn how its ring architecture abets function. Protein dynamic simulations showed its peripheral kinase domains (KDs) are conformationally coupled via lateral spread along the central hub. The underlying β-sheet motions in the hub or association domain (AD) were deconvolved into dynamic couplings based on mutual information. They mapped onto a coevolved residue network to partition the AD into two distinct sectors. A second, energetically stressed sector was added to ancient bacterial enzyme dimers for assembly of the ringed hub. The continued evolution of the holoenzyme after AD–KD fusion targeted the sector’s ring contacts coupled to the KD. Among isoforms, the α isoform emerged last and, it alone, mutated rapidly after the poikilotherm–homeotherm jump to match the evolution of memory. The correlation between dynamics and evolution of the CaMKII AD argues single residue substitutions fine-tune hub conformational spread. The fine-tuning could increase CaMKIIα Ca(2+) frequency response range for complex learning functions. Nature Publishing Group UK 2022-05-19 /pmc/articles/PMC9120016/ /pubmed/35589775 http://dx.doi.org/10.1038/s41598-022-12090-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Khan, Shahid Conformational spread drives the evolution of the calcium–calmodulin protein kinase II |
title | Conformational spread drives the evolution of the calcium–calmodulin protein kinase II |
title_full | Conformational spread drives the evolution of the calcium–calmodulin protein kinase II |
title_fullStr | Conformational spread drives the evolution of the calcium–calmodulin protein kinase II |
title_full_unstemmed | Conformational spread drives the evolution of the calcium–calmodulin protein kinase II |
title_short | Conformational spread drives the evolution of the calcium–calmodulin protein kinase II |
title_sort | conformational spread drives the evolution of the calcium–calmodulin protein kinase ii |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9120016/ https://www.ncbi.nlm.nih.gov/pubmed/35589775 http://dx.doi.org/10.1038/s41598-022-12090-y |
work_keys_str_mv | AT khanshahid conformationalspreaddrivestheevolutionofthecalciumcalmodulinproteinkinaseii |