Structural insights into “acid blobs and negative noodles” – The androgen receptor as a case study
[eng] Androgen receptor is a transcription factor that plays a key role in prostate cancer development and progression. Its N-terminal intrinsically disordered activation domain is an example of ill- structured negatively charged "acid blob" or "negative noodle" described in 1988...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/148840 |
| Acceso en línea: | https://hdl.handle.net/2445/148840 http://hdl.handle.net/10803/668406 |
| Access Level: | acceso abierto |
| Palabra clave: | Factors de transcripció Càncer de pròstata Andrògens Proteïnes Transcription factors Prostate cancer Androgens Proteins |
| Sumario: | [eng] Androgen receptor is a transcription factor that plays a key role in prostate cancer development and progression. Its N-terminal intrinsically disordered activation domain is an example of ill- structured negatively charged "acid blob" or "negative noodle" described in 1988 by Paul B. Sigler. In his model the transcription pre-initiation complex formation relies on non-specific interactions between the "negative noodles" of the transcriptional activating proteins and hydroxyl groups of the heptapeptide repeats of the C-terminal domain in the largest subunit of RNA polymerase II. Here, we take advantage of various biophysical methods to understand the AR activation domain characteristics, its ability to undergo liquid-liquid phase separation and the importance of both for protein-protein interactions of the domain. We show relevance of the secondary structure elements in the AD function despite its general "acid blob" character. |
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