Piepoli, Sofia, Alt, Aaron Oliver, Atilgan, Canan, Mancini, Erika Jazmin and Erman, Batu (2020) Structural analysis of the PATZ1 BTB domain homodimer. Acta Crystallographica Section D: Structural Biology, 76. pp. 581-593. ISSN 2059-7983

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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.

Item Type:	Article
Keywords:	BTB, PATZ1, POZ, co-repressors, dimerization interface, structure dynamics, transcription factors
Schools and Departments:	School of Life Sciences > Biochemistry
SWORD Depositor:	Mx Elements Account
Depositing User:	Mx Elements Account
Date Deposited:	25 Sep 2020 10:49
Last Modified:	16 Mar 2022 12:10
URI:	http://sro.sussex.ac.uk/id/eprint/93945

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