HCF-1 self-association via an interdigitated Fn3 structure facilitates transcriptional regulatory complex formation

Abstract

Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N-(HCF-1N) and C- (HCF-1C) terminal subunits noncovalently associated via self-association sequence elements. Here, we present the crystal structure of the self-association sequence 1 (SAS1) including the adjacent C-terminal HCF-1 nuclear localization signal (NLS). SAS1 elements from each of the HCF-1 N and HCF-1C subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure. We show that the C-terminal NLS recruited by the interdigitated SAS1 structure is required for effective formation of a transcriptional regulatory complex: the herpes simplex virus VP16-induced complex. Thus, HCF-1N-HCF-1C association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.