The crystal structure of a partial mouse Notch-1 ankyrin domain: repeats 4 through 7 preserve an ankyrin fold

Protein Sci. 2005 May;14(5):1274-81. doi: 10.1110/ps.041184105. Epub 2005 Mar 31.

Abstract

Folding and stability of proteins containing ankyrin repeats (ARs) is of great interest because they mediate numerous protein-protein interactions involved in a wide range of regulatory cellular processes. Notch, an ankyrin domain containing protein, signals by converting a transcriptional repression complex into an activation complex. The Notch ANK domain is essential for Notch function and contains seven ARs. Here, we present the 2.2 A crystal structure of ARs 4-7 from mouse Notch 1 (m1ANK). These C-terminal repeats were resistant to degradation during crystallization, and their secondary and tertiary structures are maintained in the absence of repeats 1-3. The crystallized fragment adopts a typical ankyrin fold including the poorly conserved seventh AR, as seen in the Drosophila Notch ANK domain (dANK). The structural preservation and stability of the C-terminal repeats shed a new light onto the mechanism of hetero-oligomeric assembly during Notch-mediated transcriptional activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Crystallography, X-Ray
  • Mice
  • Molecular Sequence Data
  • Protein Conformation
  • Receptor, Notch1
  • Receptors, Cell Surface / chemistry*
  • Sequence Homology, Amino Acid
  • Transcription Factors / chemistry*

Substances

  • Notch1 protein, mouse
  • Receptor, Notch1
  • Receptors, Cell Surface
  • Transcription Factors