Structure, function, and activator-induced conformations of the CRSP coactivator
- PMID: 11834832
- DOI: 10.1126/science.1065249
Structure, function, and activator-induced conformations of the CRSP coactivator
Abstract
The human cofactor complexes ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1 activation) mediate activator-dependent transcription in vitro. Although these complexes share several common subunits, their structural and functional relationships remain unknown. Here, we report that affinity-purified ARC consists of two distinct multisubunit complexes: a larger complex, denoted ARC-L, and a smaller coactivator, CRSP. Reconstituted in vitro transcription with biochemically separated ARC-L and CRSP reveals differential cofactor functions. The ARC-L complex is transcriptionally inactive, whereas the CRSP complex is highly active. Structural determination by electron microscopy (EM) and three-dimensional reconstruction indicate substantial differences in size and shape between ARC-L and CRSP. Moreover, EM analysis of independently derived CRSP complexes reveals distinct conformations induced by different activators. These results suggest that CRSP may potentiate transcription via specific activator-induced conformational changes.
Comment in
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Transcription. Mediator meets morpheus.Science. 2002 Feb 8;295(5557):984-5. doi: 10.1126/science.1069485. Science. 2002. PMID: 11834806 No abstract available.
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