Structural analysis of the PATZ1 BTB domain homodimer.

Sofia Piepoli,Batu Erman,Aaron Oliver Alt,Canan Atilgan,Erika Jazmin Mancini

doi:10.1107/s2059798320005355

Abstract

PATZ1 is a ubiquitously expressed transcriptional repressor belonging to the ZBTB family that is functionally expressed in T lymphocytes. PATZ1 targets the CD8 gene in lymphocyte development and interacts with the p53 protein to control genes that are important in proliferation and in the 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 Å resolution, respectively. The structures revealed that the PATZ1 BTB domain forms a stable homodimer with a lateral surface groove, as in other ZBTB structures. Analysis of the lateral groove revealed a large acidic patch in this region, which contrasts with the previously resolved basic co-repressor binding interface of BCL6. A large 30-amino-acid glycine- and alanine-rich central loop, which is unique to mammalian PATZ1 amongst all ZBTB proteins, could not be resolved, probably owing to its flexibility. Molecular-dynamics simulations suggest a contribution of this loop to modulation of the mammalian BTB dimerization interface.

Highlights

PATZ1 (POZ, AT hook- and zinc-finger-containing protein 1), known as ZBTB19, is a transcription factor that is present in all vertebrates (Fig. 1a)
In a similar way to other members of the ZBTB family, both PATZ1 BTB crystal structures reveal a strand-exchange homodimer, organized as a core fold BTB domain preceded by an N-terminal extension that interacts with the partner chain in the dimer
Size-exclusion chromatography data for both the murine and zebrafish BTB domains suggest that the homodimeric complex is the most abundant oligomerization state found in solution (Supplementary Fig. S1)

Summary

Introduction

PATZ1 (POZ-, AT hook- and zinc-finger-containing protein 1), known as ZBTB19, is a transcription factor that is present in all vertebrates (Fig. 1a). It was first discovered in a yeast two-hybrid (Y2H) experiment, in which it associated through its BTB (broad complex, tramtrack and bric-a-brac) domain with the BTB domain of the transcription factor BACH2 (BTB and CNC homology 2; Kobayashi et al, 2000). While its expression can be detected in many cell types and developmental stages, PATZ1/ZBTB19/MAZR is highly expressed in the early stages of T-lymphocyte differentiation, where it negatively regulates CD8 gene expression (Bilic & Ellmeier, 2007).

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Results

Conclusion