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Structural dynamics shape the fitness window of alanine:glyoxylate aminotransferase
https://oist.repo.nii.ac.jp/records/2642
https://oist.repo.nii.ac.jp/records/26424edb7264-a4c8-4456-960b-91c40dd3acfd
名前 / ファイル | ライセンス | アクション |
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Dindo-2022-Structural dynamics shape the fitne (3.9 MB)
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Creative Commons Attribution 4.0 International (https://creativecommons.org/licenses/by/4.0/)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2022-05-19 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Structural dynamics shape the fitness window of alanine:glyoxylate aminotransferase | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | alanine:glyoxylate aminotransferases | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | conformational plasticity | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | protein evolution | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | protein fitness | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | structural dynamics | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者(英) |
Dindo, Mirco
× Dindo, Mirco× Pascarelli, Stefano× Chiasserini, Davide× Grottelli, Silvia× Costantini, Claudio× Uechi, Gen‐Ichiro× Giardina, Giorgio× Laurino, Paola× Cellini, Barbara |
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書誌情報 |
en : Protein Science 巻 31, 号 5, p. e4303, 発行日 2022-04-11 |
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抄録 | ||||||
内容記述タイプ | Other | |||||
内容記述 | The conformational landscape of a protein is constantly expanded by genetic variations that have a minimal impact on the function(s) while causing subtle effects on protein structure. The wider the conformational space sampled by these variants, the higher the probabilities to adapt to changes in environmental conditions. However, the probability that a single mutation may result in a pathogenic phenotype also increases. Here we present a paradigmatic example of how protein evolution balances structural stability and dynamics to maximize protein adaptability and preserve protein fitness. We took advantage of known genetic variations of human alanine:glyoxylate aminotransferase (AGT1), which is present as a common major allelic form (AGT-Ma) and a minor polymorphic form (AGT-Mi) expressed in 20% of Caucasian population. By integrating crystallographic studies and molecular dynamics simulations, we show that AGT-Ma is endowed with structurally unstable (frustrated) regions, which become disordered in AGT-Mi. An in-depth biochemical characterization of variants from an anticonsensus library, encompassing the frustrated regions, correlates this plasticity to a fitness window defined by AGT-Ma and AGT-Mi. Finally, co-immunoprecipitation analysis suggests that structural frustration in AGT1 could favor additional functions related to protein-protein interactions. These results expand our understanding of protein structural evolution by establishing that naturally occurring genetic variations tip the balance between stability and frustration to maximize the ensemble of conformations falling within a well-defined fitness window, thus expanding the adaptability potential of the protein. | |||||
出版者 | ||||||
出版者 | Wiley Periodicals LLC on behalf of The Protein Society. | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0961-8368 | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 1469-896X | |||||
PubMed番号 | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | info:pmid/35481644 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1002/pro.4303 | |||||
権利 | ||||||
権利情報 | © 2022 The Authors. | |||||
関連サイト | ||||||
識別子タイプ | URI | |||||
関連識別子 | https://onlinelibrary.wiley.com/doi/10.1002/pro.4303 | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 |