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  Crosstalk between regulatory elements in disordered TRPV4 N-terminus modulates lipid-dependent channel activity

Goretzki, B., Wiedemann, C., McCray, B. A., Schäfer, S. L., Jansen, J., Tebbe, F., Mitrovic, S.-A., Nöth, J., Cabezudo, A. C., Donohue, J. K., Jeffries, C. M., Steinchen, W., Stengel, F., Sumner, C. J., Hummer, G., & Hellmich, U. A. (2023). Crosstalk between regulatory elements in disordered TRPV4 N-terminus modulates lipid-dependent channel activity. Nature Communications, 14:. doi:10.1038/s41467-023-39808-4.

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アイテムのパーマリンク: https://hdl.handle.net/21.11116/0000-000D-7338-3 版のパーマリンク: https://hdl.handle.net/21.11116/0000-000E-4CBA-C
資料種別: 学術論文

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 作成者:
Goretzki, Benedikt1, 2, 著者
Wiedemann, Christoph1, 著者
McCray, Brett A.3, 著者
Schäfer, Stefan L.4, 著者                 
Jansen, Jasmin5, 6, 著者
Tebbe, Frederike1, 著者
Mitrovic, Sarah-Ana7, 著者
Nöth, Julia7, 著者
Cabezudo, Ainara Claveras4, 8, 著者                 
Donohue, Jack K.3, 著者
Jeffries, Cy M.9, 著者
Steinchen, Wieland10, 著者
Stengel, Florian5, 6, 著者
Sumner, Charlotte J.3, 11, 著者
Hummer, Gerhard4, 12, 著者                 
Hellmich, Ute A.1, 2, 13, 著者
所属:
1Friedrich Schiller University Jena, Faculty of Chemistry and Earth Sciences, Institute of Organic Chemistry and Macromolecular Chemistry, Jena, Germany, ou_persistent22              
2Centre for Biomolecular Magnetic Resonance (BMRZ), Goethe University, Frankfurt am Main, Germany, ou_persistent22              
3Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA, ou_persistent22              
4Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max Planck Society, ou_2068292              
5Department of Biology, University of Konstanz, Konstanz, Germany, ou_persistent22              
6Konstanz Research School Chemical Biology, University of Konstanz, Konstanz, Germany, ou_persistent22              
7Department of Chemistry, Section Biochemistry, Johannes Gutenberg-University Mainz, Mainz, Germany, ou_persistent22              
8IMPRS-CBP, Max Planck Institute of Biophysics, Max Planck Society, ou_3562496              
9European Molecular Biology Laboratory, EMBL Hamburg Unit, Deutsches Elektronen-Synchrotron, Hamburg, Germany, ou_persistent22              
10Center for Synthetic Microbiology (SYNMIKRO) & Department of Chemistry, Philipps-University Marburg, Marburg, Germany, ou_persistent22              
11Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA, ou_persistent22              
12Institute of Biophysics, Goethe University Frankfurt, Frankfurt am Main, Germany, ou_persistent22              
13Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany, ou_persistent22              

内容説明

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キーワード: Biophysics, Transient receptor potential channels
 要旨: Intrinsically disordered regions (IDRs) are essential for membrane receptor regulation but often remain unresolved in structural studies. TRPV4, a member of the TRP vanilloid channel family involved in thermo- and osmosensation, has a large N-terminal IDR of approximately 150 amino acids. With an integrated structural biology approach, we analyze the structural ensemble of the TRPV4 IDR and the network of antagonistic regulatory elements it encodes. These modulate channel activity in a hierarchical lipid-dependent manner through transient long-range interactions. A highly conserved autoinhibitory patch acts as a master regulator by competing with PIP2 binding to attenuate channel activity. Molecular dynamics simulations show that loss of the interaction between the PIP2-binding site and the membrane reduces the force exerted by the IDR on the structured core of TRPV4. This work demonstrates that IDR structural dynamics are coupled to TRPV4 activity and highlights the importance of IDRs for TRP channel function and regulation.

資料詳細

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言語: eng - English
 日付: 2022-12-212023-06-272023-07-13
 出版の状態: オンラインで出版済み
 ページ: 20
 出版情報: -
 目次: -
 査読: 査読あり
 識別子（DOI, ISBNなど）: DOI: 10.1038/s41467-023-39808-4
BibTex参照ID: goretzki_crosstalk_2023
 学位: -

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出版物 1

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出版物名: Nature Communications
  省略形 : Nat. Commun.
種別: 学術雑誌
 著者・編者:
所属:
出版社, 出版地: London : Nature Publishing Group
ページ: - 巻号: 14 通巻号: 4165 開始・終了ページ: - 識別子（ISBN, ISSN, DOIなど）: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723