Mathony, Jan ; Aschenbrenner, Sabine ; Becker, Philipp ; Niopek, Dominik (2024)
Dissecting the Determinants of Domain Insertion Tolerance and Allostery in Proteins.
In: Advanced Science, 2023, 10 (28)
doi: 10.26083/tuprints-00027224
Artikel, Zweitveröffentlichung, Verlagsversion
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Kurzbeschreibung (Abstract)
Domain insertion engineering is a promising approach to recombine the functions of evolutionarily unrelated proteins. Insertion of light‐switchable receptor domains into a selected effector protein, for instance, can yield allosteric effectors with light‐dependent activity. However, the parameters that determine domain insertion tolerance and allostery are poorly understood. Here, an unbiased screen is used to systematically assess the domain insertion permissibility of several evolutionary unrelated proteins. Training machine learning models on the resulting data allow to dissect features informative for domain insertion tolerance and revealed sequence conservation statistics as the strongest indicators of suitable insertion sites. Finally, extending the experimental pipeline toward the identification of switchable hybrids results in opto‐chemogenetic derivatives of the transcription factor AraC that function as single‐protein Boolean logic gates. The study reveals determinants of domain insertion tolerance and yielded multimodally switchable proteins with unique functional properties.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2024 |
| Autor(en): | Mathony, Jan ; Aschenbrenner, Sabine ; Becker, Philipp ; Niopek, Dominik |
| Art des Eintrags: | Zweitveröffentlichung |
| Titel: | Dissecting the Determinants of Domain Insertion Tolerance and Allostery in Proteins |
| Sprache: | Englisch |
| Publikationsjahr: | 27 Mai 2024 |
| Ort: | Darmstadt |
| Publikationsdatum der Erstveröffentlichung: | 6 Oktober 2023 |
| Ort der Erstveröffentlichung: | Weinheim |
| Verlag: | Wiley-VCH |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Advanced Science |
| Jahrgang/Volume einer Zeitschrift: | 10 |
| (Heft-)Nummer: | 28 |
| Kollation: | 13 Seiten |
| DOI: | 10.26083/tuprints-00027224 |
| URL / URN: | https://tuprints.ulb.tu-darmstadt.de/27224 |
| Zugehörige Links: | |
| Herkunft: | Zweitveröffentlichung DeepGreen |
| Kurzbeschreibung (Abstract): | Domain insertion engineering is a promising approach to recombine the functions of evolutionarily unrelated proteins. Insertion of light‐switchable receptor domains into a selected effector protein, for instance, can yield allosteric effectors with light‐dependent activity. However, the parameters that determine domain insertion tolerance and allostery are poorly understood. Here, an unbiased screen is used to systematically assess the domain insertion permissibility of several evolutionary unrelated proteins. Training machine learning models on the resulting data allow to dissect features informative for domain insertion tolerance and revealed sequence conservation statistics as the strongest indicators of suitable insertion sites. Finally, extending the experimental pipeline toward the identification of switchable hybrids results in opto‐chemogenetic derivatives of the transcription factor AraC that function as single‐protein Boolean logic gates. The study reveals determinants of domain insertion tolerance and yielded multimodally switchable proteins with unique functional properties. |
| Freie Schlagworte: | allostery, domain insertion, optogenetics, protein engineering |
| ID-Nummer: | Artikel-ID: 2303496 |
| Status: | Verlagsversion |
| URN: | urn:nbn:de:tuda-tuprints-272242 |
| Sachgruppe der Dewey Dezimalklassifikatin (DDC): | 500 Naturwissenschaften und Mathematik > 570 Biowissenschaften, Biologie 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin, Gesundheit |
| Fachbereich(e)/-gebiet(e): | Interdisziplinäre Forschungsprojekte Interdisziplinäre Forschungsprojekte > Centre for Synthetic Biology |
| Hinterlegungsdatum: | 27 Mai 2024 13:10 |
| Letzte Änderung: | 03 Jun 2024 11:58 |
| PPN: | |
| Export: | |
| Suche nach Titel in: | TUfind oder in Google |
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- Dissecting the Determinants of Domain Insertion Tolerance and Allostery in Proteins. (deposited 27 Mai 2024 13:10) [Gegenwärtig angezeigt]
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