Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation

Kay Fukushima, Jun Kikuchi, Seizo Koshiba, Takanori Kigawa, Yutaka Kuroda, Shigeyuki Yokoyama

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

DFF45/ICAD has dual functions in the final stage of apoptosis, by acting as both a folding chaperone and a DNase inhibitor of DFF40/CAD. Here, we present the solution structure of the C-terminal domain of DFF45, which is essential for its chaperone-like activity. The structure of this domain (DFF-C) consists of four α helices, which are folded in a novel helix-packing arrangement. The 3D structure reveals a large cluster of negatively charged residues on the molecular surface of DFF-C. This observation suggests that charge complementation plays an important role in the interaction of DFF-C with the positively charged catalytic domain of DFF40, and thus for the chaperone activity of DFF45. The structure of DFF-C also provides a rationale for the loss of the chaperone activity in DFF35, a short isoform of DFF45. Indeed, in DFF35, the amino acid sequence is truncated in the middle of the second α helix constituting the structure of DFF-C, and thus both the hydrophobic core and the cluster of negative charges are disrupted.

Original languageEnglish
Pages (from-to)317-327
Number of pages11
JournalJournal of Molecular Biology
Volume321
Issue number2
DOIs
Publication statusPublished - 2002
Externally publishedYes

Keywords

  • Apoptosis
  • Chaperone-like activity
  • DREP-1
  • NMR
  • Stable domain

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Fingerprint

Dive into the research topics of 'Solution structure of the DFF-C domain of DFF45/ICAD. A structural basis for the regulation of apoptotic DNA fragmentation'. Together they form a unique fingerprint.

Cite this