Solution NMR structure of the C-terminal domain of the human protein DEK

Matthew Devany, N. Prasad Kotharu, Hiroshi Matsuo

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2252-2259
Number of pages8
JournalProtein Science
Volume13
Issue number8
DOIs
StatePublished - Aug 2004

Keywords

  • Acute myeloid leukemia
  • Ataxia-telangiectasia
  • Chromatin-associated protein
  • Chromosomal translocation
  • NMR structure
  • Oncogene product

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