Structure, function, and activator-induced conformations of the CRSP coactivator.

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.
Mesh Terms:
CCAAT-Enhancer-Binding Proteins, Chromatin, DNA-Binding Proteins, Hela Cells, Herpes Simplex Virus Protein Vmw65, Humans, Image Processing, Computer-Assisted, Imaging, Three-Dimensional, Macromolecular Substances, Microscopy, Electron, Models, Genetic, Precipitin Tests, Protein Binding, Protein Structure, Quaternary, Protein Structure, Tertiary, Protein Subunits, Recombinant Fusion Proteins, Recombinant Proteins, Sterol Regulatory Element Binding Protein 1, Trans-Activators, Transcription Factors, Transcription, Genetic, Transcriptional Activation
Science
Date: Feb. 08, 2002
Download Curated Data For This Publication
124774
Switch View:
  • Interactions 13