Solution structure of ASPP2 N-terminal domain (N-ASPP2) reveals a ubiquitin-like fold

J Mol Biol. 2007 Aug 24;371(4):948-58. doi: 10.1016/j.jmb.2007.05.024. Epub 2007 May 13.

Abstract

Proteins of the ASPP family bind to p53 and regulate p53-mediated apoptosis. Two family members, ASPP1 and ASPP2, have pro-apoptotic functions while iASPP shows anti-apoptotic responses. However, both the mechanism of enhancement/repression of apoptosis and the molecular basis for their different responses remain unknown. To address the role of the N-termini of pro-apoptotic ASPP proteins, we solved the solution structure of N-ASPP2 (1-83) by NMR spectroscopy. The structure of this domain reveals a beta-Grasp ubiquitin-like fold. Our findings suggest a possible role for the N-termini of ASPP proteins in binding to other proteins in the apoptotic response network and thus mediating their selective pro-apoptotic function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Circular Dichroism
  • Conserved Sequence
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Denaturation
  • Protein Folding*
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Temperature
  • Ubiquitin / chemistry*
  • Ubiquitin / classification
  • Ubiquitin / metabolism*

Substances

  • Apoptosis Regulatory Proteins
  • Carrier Proteins
  • TP53BP2 protein, human
  • Ubiquitin

Associated data

  • PDB/2UWQ