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Solution NMR structure of the C‐terminal domain of the human protein DEK
Author(s) -
Devany Matthew,
Kotharu N. Prasad,
Matsuo Hiroshi
Publication year - 2004
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 - 10.1110/ps.04797104
Subject(s) - fusion protein , dna , chromatin , ataxia telangiectasia , nuclear magnetic resonance spectroscopy , biology , phd finger , chemistry , genetics , microbiology and biotechnology , transcription factor , dna damage , gene , stereochemistry , recombinant dna , zinc finger
The chromatin‐associated protein DEK was first identified as a fusion protein in patients with a subtype of acute myelogenous leukemia. It has since become associated with diverse human ailments ranging from cancers to autoimmune diseases. Despite much research effort, the biochemical basis for these clinical connections has yet to be explained. We have identified a structural domain in the C‐terminal region of DEK [DEK(309–375)]. DEK(309–375) implies clinical importance because it can reverse the characteristic abnormal DNA‐mutagen sensitivity in fibroblasts from ataxia‐telangiectasia (A‐T) patients. We determined the solution structure of DEK(309–375) by nuclear magnetic resonance spectroscopy, and found it to be structurally homologous to the E2F/DP transcription factor family. On the basis of this homology, we tested whether DEK(309–375) could bind DNA and identified the DNA‐interacting surface. DEK presents a hydrophobic surface on the side opposite the DNA‐interacting surface. The structure of the C‐terminal region of DEK provides insights into the protein function of DEK.