PUBLICATION

Structural analysis of the PATZ1 BTB domain homodimer

Authors
Piepoli, S., Alt, A.O., Atilgan, C., Mancini, E.J., Erman, B.
ID
ZDB-PUB-200606-10
Date
2020
Source
Acta crystallographica. Section D, Structural biology   76: 581-593 (Journal)
Registered Authors
Keywords
BTB, PATZ1, POZ, co-repressors, dimerization interface, structure dynamics, transcription factors
MeSH Terms
  • Repressor Proteins/chemistry*
  • Zebrafish Proteins/chemistry*
  • Zebrafish/metabolism
  • Neoplasm Proteins/chemistry*
  • Animals
  • Mice
  • Protein Multimerization
  • BTB-POZ Domain*
PubMed
32496219 Full text @ Acta Crystallogr D Struct Biol
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.
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