Solution NMR structure of the C-terminal domain of the human protein DEK.
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.
Devany
Matthew
M
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Kotharu
N Prasad
NP
Matsuo
Hiroshi
H
D001260:Ataxia Telangiectasia / Q000378:metabolism; D001327:Autoimmune Diseases / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism; D016296:Mutagenesis; D019906:Nuclear Magnetic Resonance, Biomolecular; D015513:Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism; D000075223:Poly-ADP-Ribose Binding Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D014157:Transcription Factors / Q000737:chemistry
D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D014157:Transcription Factors; D004247:DNA