title: A combinatorial method to enable detailed investigation of protein-protein interactions.
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.
  
  
  CONCLUSIONS
  This resource-efficient process can provide protein complexes for screening of compounds designed to modulate protein-protein interactions, thus facilitating novel drug discovery.
authors: The Institute of Structural & Molecular Biology, Research Department of Structural & Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK.
authors: Kate
authors: K
authors: Maclagan
authors: Rita
authors: R
authors: Tommasi
authors: Emmanuelle
authors: E
authors: Laurine
authors: Chrisostomos
authors: C
authors: Prodromou
authors: Paul C
authors: PC
authors: Driscoll
authors: Laurence H
authors: LH
authors: Pearl
authors: Stefanie
authors: S
authors: Reich
authors: Renos
authors: R
authors: Savva
mesh_terms: D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D018833:Chaperonins / Q000737:chemistry* / Q000378:metabolism; D055808:Drug Discovery / Q000379:methods*; D004926:Escherichia coli; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D046912:Multiprotein Complexes / Q000737:chemistry; D019151:Peptide Library; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000379:methods*; D011994:Recombinant Proteins / Q000096:biosynthesis
chemical_list: C498362:CDC37 protein, human; D018797:Cell Cycle Proteins; D018841:HSP90 Heat-Shock Proteins; C493165:HSP90AB1 protein, human; D046912:Multiprotein Complexes; D019151:Peptide Library; D011994:Recombinant Proteins; D018833:Chaperonins