PNAS; co-auth.: group Herr

Proc Natl Acad Sci U S A. 2012 Oct 8. [Epub ahead of print]

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


Department of Biological Sciences and Graduate School of Nanoscience and Technology (World Class University), KAIST (Korea Advanced Institute of Science and Technology) Institute for the BioCentury, KAIST, Daejeon 305-701, Korea.


Host-cell factor 1 (HCF-1) is an unusual transcriptional regulator that undergoes a process of proteolytic maturation to generate N- (HCF-1(N)) and C- (HCF-1(C)) 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-1(C) 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-1(N)-HCF-1(C) association via an integrated Fn3 structure permits an NLS to facilitate formation of a transcriptional regulatory complex.