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Biophysical characterization of the breast cancer-related BIG3-PHB2 interaction: Effect of non-conserved loop region of BIG3 on the structure and the interaction.

Abstract
Brefeldin A-inhibited guanine nucleotide-exchange protein 3 (BIG3) interacts with and inhibits the tumor suppressor function of prohibitin-2 (PHB2), and recent in vivo studies have demonstrated that the BIG3-PHB2 interaction is a promising target for breast cancer therapy. However, little biophysical characterization on BIG3 and its interaction with PHB2 has been reported. Here we compared the calculated 8-class secondary structure of the N-terminal domains of BIG family proteins and identified a loop region unique to BIG3. Our biophysical characterization demonstrated that this loop region significantly affects the colloidal and thermodynamic stability of BIG3 and the thermodynamic and kinetic profile of its interaction with PHB2. These results establish a model for the BIG3-PHB2 interaction and an entry for drug discovery for breast cancer.
AuthorsTakeru Chigira, Satoru Nagatoishi, Hiroyuki Takeda, Tetsuro Yoshimaru, Toyomasa Katagiri, Kouhei Tsumoto
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 518 Issue 1 Pg. 183-189 (10 08 2019) ISSN: 1090-2104 [Electronic] United States
PMID31421830 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2019 Elsevier Inc. All rights reserved.
Chemical References
  • ARFGEF3 protein, human
  • Colloids
  • Guanine Nucleotide Exchange Factors
  • PHB2 protein, human
  • Prohibitins
  • Recombinant Proteins
  • Repressor Proteins
Topics
  • Amino Acid Sequence
  • Biophysical Phenomena
  • Breast Neoplasms (metabolism)
  • Colloids (chemistry)
  • Conserved Sequence
  • Female
  • Guanine Nucleotide Exchange Factors (chemistry, metabolism)
  • Humans
  • Kinetics
  • Models, Biological
  • Prohibitins
  • Protein Binding
  • Protein Domains
  • Protein Stability
  • Protein Structure, Secondary
  • Recombinant Proteins (metabolism)
  • Repressor Proteins (metabolism)
  • Structure-Activity Relationship
  • Temperature

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