Structure, Function, and Activator-Induced Conformations of the CRSP Coactivator

• DOI: 10.1126/science.1065249
• Publication Date: 2002-07-27T09:35:18Z
• Authors: Dylan J. Taatjes; Anders M. Näär; Frank Andel; Eva Nogales; Robert Tjian
• Keywords: Transcription

The human cofactor complexes ARC (activator-recruited cofactor) and CRSP (cofactor required for Sp1 activation) mediate activator-dependent transcription in vitro. Although these share several common subunits, their structural functional relationships remain unknown. Here, we report that affinity-purified consists of two distinct multisubunit complexes: a larger complex, denoted ARC-L, smaller coactivator, CRSP. Reconstituted vitro with biochemically separated ARC-L reveals differential functions. complex is transcriptionally inactive, whereas the highly active. Structural determination by electron microscopy (EM) three-dimensional reconstruction indicate substantial differences size shape between Moreover, EM analysis independently derived conformations induced different activators. These results suggest may potentiate via specific activator-induced conformational changes.