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Insights from the crystal structure of the sixth BRCT domain of topoisomerase IIβ binding protein 1
Author(s) -
Leung Charles Chung Yun,
Kellogg Elizabeth,
Kuhnert Anja,
Hänel Frank,
Baker David,
Glover J. N. Mark
Publication year - 2010
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.290
Subject(s) - binding site , biology , poly adp ribose polymerase , binding domain , polymerase , hmg box , protein structure , biophysics , transcription factor , microbiology and biotechnology , dna , biochemistry , chemistry , dna binding protein , gene
Topoisomerase IIβ binding protein 1 (TopBP1) is a major player in the DNA damage response and interacts with a number of protein partners via its eight BRCA1 carboxy‐terminal (BRCT) domains. In particular, the sixth BRCT domain of TopBP1 has been implicated in binding to the phosphorylated transcription factor, E2F1, and poly(ADP‐ribose) polymerase 1 (PARP‐1), where the latter interaction is responsible for the poly(ADP‐ribosyl)ation of TopBP1. To gain a better understanding of the nature of TopBP1 BRCT6 interactions, we solved the crystal structure of BRCT6 to 1.34 Å. The crystal structure reveals a degenerate phospho‐peptide binding pocket and lacks conserved hydrophobic residues involved in packing of tandem BRCT repeats, which, together with results from phospho‐peptide binding studies, strongly suggest that TopBP1 BRCT6 independently does not function as a phospho‐peptide binding domain. We further provide insight into poly(ADP‐ribose) binding and sites of potential modification by PARP‐1.