Structural Analysis of the PATZ1 BTB domain homodimer

Abstract

PATZ1 is a transcriptional repressor belonging to the ZBTB family that is functionally expressed in T-lymphocytes, as well as in a ubiquitous fashion. PATZ1 targets the Cd8 gene in lymphocyte development and interacts with the p53 protein to control genes important in proliferation and DNA damage response. PATZ1 exerts its activity through an N-terminal BTB domain that mediates dimerization and co-repressor interactions and a C-terminal zinc finger motif-containing domain that mediates DNA binding. Here, the crystal structures of the murine and zebrafish PATZ1 BTB domains are reported at 2.3 and 1.8 [A] resolution respectively. The structures reveal that, like other ZBTB structures, the PATZ1 BTB domain forms a stable homodimer and likely binds co-repressors through a lateral surface groove that is formed upon dimerization. Analysis of the lateral groove reveals a large acidic patch in this region which contrasts previously resolved basic co-repressor binding interfaces in other ZBTB proteins. A large 30 amino acids glycine- and alanine-rich central loop, unique to mammalian PATZ1 amongst all ZBTB proteins, could not be resolved likely due to its flexibility. Modelling of this loop indicates that it can participate in the dimerization interface of BTB monomers. SynopsisThe crystal structures of the PATZ1 BTB domain in mammals and fish are homodimers. The core dimer conformation of these BTB proteins is dynamically stable, despite the presence of highly flexible regions in the dimerization interface.