A combinatorial method to enable detailed investigation of protein-protein interactions

Future Med Chem. 2011 Mar;3(3):271-82. doi: 10.4155/fmc.10.289.

Abstract

Background: Successful structural investigations of protein-protein interactions can be facilitated by studying only the core interacting regions of the constituent proteins. However, attempting the discovery of stable core complexes using informed trial-and-error approaches can prove time and resource intensive.

Methods: We describe a valuable extension of combinatorial domain hunting (CDH), a technology for the timely elucidation of soluble protein truncations. The new method, CDH(2), enables empirical discovery of stable protein-protein core complexes. CDH(2) is demonstrated ab initio using a previously well-characterized Hsp90/Cdc37 complex.

Results: Without using a priori information, we demonstrate the isolation of stable protein-protein complexes, suitable for further analyses.

Discussion: This resource-efficient process can provide protein complexes for screening of compounds designed to modulate protein-protein interactions, thus facilitating novel drug discovery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Cell Cycle Proteins / chemistry*
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • Chaperonins / chemistry*
  • Chaperonins / metabolism
  • Drug Discovery / methods*
  • Escherichia coli
  • HSP90 Heat-Shock Proteins / chemistry*
  • HSP90 Heat-Shock Proteins / metabolism
  • Humans
  • Multiprotein Complexes / chemistry
  • Peptide Library
  • Protein Interaction Domains and Motifs*
  • Protein Interaction Mapping / methods*
  • Recombinant Proteins / biosynthesis

Substances

  • CDC37 protein, human
  • Cell Cycle Proteins
  • HSP90 Heat-Shock Proteins
  • HSP90AB1 protein, human
  • Multiprotein Complexes
  • Peptide Library
  • Recombinant Proteins
  • Chaperonins