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Structural analysis of the PATZ1 BTB domain homodimer

DOI: 10.1107/S2059798320005355 DOI Help

Authors: Sofia Piepoli (Sabanci University) , Aaron Oliver Alt (University of Sussex) , Canan Atilgan (Sabanci University) , Erika Jazmin Mancini (University of Oxford) , Batu Erman (Sabanci University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acta Crystallographica Section D Structural Biology , VOL 76 , PAGES 581 - 593

State: Published (Approved)
Published: June 2020
Diamond Proposal Number(s): 20145

Open Access Open Access

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.

Journal Keywords: BTB; POZ; PATZ1; transcription factors; co-repressors; dimerization interface; structure dynamics

Subject Areas: Biology and Bio-materials


Instruments: I04-Macromolecular Crystallography

Added On: 24/06/2020 14:40

Documents:
ni5006.pdf

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)