Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation
Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide segments that fail to form stable 3-dimensional structures in the absence of partner proteins. They are abundant in eukaryotic proteomes and are often associated with human diseases, but their biological functions have bee...
| Main Authors: | , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
eLife Sciences Publications, Ltd.
2015
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| Online Access: | http://hdl.handle.net/1721.1/99670 |
| _version_ | 1826209056292864000 |
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| author | Zhang, Zhengjian Boskovic, Zarko Hu, Wenxin Inouye, Carla Kim, Han-Je Tjian, Robert Hussain, Mahmud M. Abole, A. Katherine Doud, Mary K. Lewis, Timothy A. Koehler, Angela Nicole Schreiber, Stuart L. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Zhang, Zhengjian Boskovic, Zarko Hu, Wenxin Inouye, Carla Kim, Han-Je Tjian, Robert Hussain, Mahmud M. Abole, A. Katherine Doud, Mary K. Lewis, Timothy A. Koehler, Angela Nicole Schreiber, Stuart L. |
| author_sort | Zhang, Zhengjian |
| collection | MIT |
| description | Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide segments that fail to form stable 3-dimensional structures in the absence of partner proteins. They are abundant in eukaryotic proteomes and are often associated with human diseases, but their biological functions have been elusive to study. In this study, we report the identification of a tin(IV) oxochloride-derived cluster that binds an evolutionarily conserved IDR within the metazoan TFIID transcription complex. Binding arrests an isomerization of promoter-bound TFIID that is required for the engagement of Pol II during the first (de novo) round of transcription initiation. However, the specific chemical probe does not affect reinitiation, which requires the re-entry of Pol II, thus, mechanistically distinguishing these two modes of transcription initiation. This work also suggests a new avenue for targeting the elusive IDRs by harnessing certain features of metal-based complexes for mechanistic studies, and for the development of novel pharmaceutical interventions. |
| first_indexed | 2024-09-23T14:16:58Z |
| format | Article |
| id | mit-1721.1/99670 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:16:58Z |
| publishDate | 2015 |
| publisher | eLife Sciences Publications, Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/996702022-09-28T19:42:00Z Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation Zhang, Zhengjian Boskovic, Zarko Hu, Wenxin Inouye, Carla Kim, Han-Je Tjian, Robert Hussain, Mahmud M. Abole, A. Katherine Doud, Mary K. Lewis, Timothy A. Koehler, Angela Nicole Schreiber, Stuart L. Massachusetts Institute of Technology. Department of Biological Engineering Koch Institute for Integrative Cancer Research at MIT Koehler, Angela Nicole Intrinsically disordered proteins/regions (IDPs/IDRs) are proteins or peptide segments that fail to form stable 3-dimensional structures in the absence of partner proteins. They are abundant in eukaryotic proteomes and are often associated with human diseases, but their biological functions have been elusive to study. In this study, we report the identification of a tin(IV) oxochloride-derived cluster that binds an evolutionarily conserved IDR within the metazoan TFIID transcription complex. Binding arrests an isomerization of promoter-bound TFIID that is required for the engagement of Pol II during the first (de novo) round of transcription initiation. However, the specific chemical probe does not affect reinitiation, which requires the re-entry of Pol II, thus, mechanistically distinguishing these two modes of transcription initiation. This work also suggests a new avenue for targeting the elusive IDRs by harnessing certain features of metal-based complexes for mechanistic studies, and for the development of novel pharmaceutical interventions. National Cancer Institute (U.S.). Initiative for Chemical Genetics (Contract N01-CO-12400) National Cancer Institute (U.S.). Cancer Target Discovery and Development Network (R01 CA160860) 2015-11-02T20:40:14Z 2015-11-02T20:40:14Z 2015-08 2015-04 Article http://purl.org/eprint/type/JournalArticle 2050-084X http://hdl.handle.net/1721.1/99670 Zhang, Zhengjian, Zarko Boskovic, Mahmud M Hussain, Wenxin Hu, Carla Inouye, Han-Je Kim, A Katherine Abole, et al. “Chemical Perturbation of an Intrinsically Disordered Region of TFIID Distinguishes Two Modes of Transcription Initiation.” eLife 4 (August 28, 2015). en_US http://dx.doi.org/10.7554/eLife.07777 eLife Creative Commons Attribution http://creativecommons.org/licenses/by/4.0/ application/pdf eLife Sciences Publications, Ltd. eLife Sciences Publications, Ltd. |
| spellingShingle | Zhang, Zhengjian Boskovic, Zarko Hu, Wenxin Inouye, Carla Kim, Han-Je Tjian, Robert Hussain, Mahmud M. Abole, A. Katherine Doud, Mary K. Lewis, Timothy A. Koehler, Angela Nicole Schreiber, Stuart L. Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation |
| title | Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation |
| title_full | Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation |
| title_fullStr | Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation |
| title_full_unstemmed | Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation |
| title_short | Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation |
| title_sort | chemical perturbation of an intrinsically disordered region of tfiid distinguishes two modes of transcription initiation |
| url | http://hdl.handle.net/1721.1/99670 |
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