Insight into residues involved in the structure and function of the breast cancer associated protein human gamma synuclein

J Mol Model. 2011 Feb;17(2):251-63. doi: 10.1007/s00894-010-0718-4. Epub 2010 May 2.

Abstract

Aberrantly expressed human gamma synuclein (SNCG) interacts with BubR1 and heat shock protein 70 (Hsp70) in late stages of breast and ovarian cancer. This interaction is essential for progression, development and survival of cancer cells. A short, synthetically designed ankyrin-repeat-containing peptide (ANK peptide) was proven to inhibit the activity of SNCG. However, the potential binding site residues of SNCG responsible for its oncogenic function have not been reported so far. The objectives of this study were to generate a three-dimensional model of SNCG and to identify the key residues involved in interaction with BubR1, ANK peptide and Hsp70. Our study is the first attempt to report the specific binding of SNCG with the TPR motif of BubR1 and the 18kDa region of Hsp70. Our findings provide novel insights into the mechanism of interaction of SNCG, and can act as a basis for the ongoing drug design and discovery process aimed at treating breast and ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Ankyrins / metabolism*
  • Breast Neoplasms / metabolism*
  • Female
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Models, Molecular
  • Mutation
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / chemistry*
  • Neoplasm Proteins / metabolism*
  • Protein Conformation
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sequence Alignment
  • alpha-Synuclein / chemistry
  • gamma-Synuclein / antagonists & inhibitors
  • gamma-Synuclein / chemistry*
  • gamma-Synuclein / metabolism*

Substances

  • Ankyrins
  • HSP70 Heat-Shock Proteins
  • Neoplasm Proteins
  • SNCG protein, human
  • alpha-Synuclein
  • gamma-Synuclein
  • BUB1 protein, human
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases