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Structural analysis of the PATZ1 BTB domain homodimer
Author(s) -
Piepoli Sofia,
Alt Aaron Oliver,
Atilgan Canan,
Mancini Erika Jazmin,
Erman Batu
Publication year - 2020
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.374
H-Index - 138
ISSN - 2059-7983
DOI - 10.1107/s2059798320005355
Subject(s) - biology , repressor , gene , leucine zipper , cd69 , microbiology and biotechnology , peptide sequence , transcription factor , genetics , immune system , t cell , il 2 receptor
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.