Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors

Science. 2001 Feb 23;291(5508):1553-7. doi: 10.1126/science.1057268.


Bag (Bcl2-associated athanogene) domains occur in a class of cofactors of the eukaryotic chaperone 70-kilodalton heat shock protein (Hsp70) family. Binding of the Bag domain to the Hsp70 adenosine triphosphatase (ATPase) domain promotes adenosine 5'-triphosphate-dependent release of substrate from Hsp70 in vitro. In a 1.9 angstrom crystal structure of a complex with the ATPase of the 70-kilodalton heat shock cognate protein (Hsc70), the Bag domain forms a three-helix bundle, inducing a conformational switch in the ATPase that is incompatible with nucleotide binding. The same switch is observed in the bacterial Hsp70 homolog DnaK upon binding of the structurally unrelated nucleotide exchange factor GrpE. Thus, functional convergence has allowed proteins with different architectures to trigger a conserved conformational shift in Hsp70 that leads to nucleotide exchange.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Adenosine Triphosphatases / chemistry*
  • Adenosine Triphosphatases / metabolism*
  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism*
  • Cattle
  • Crystallography, X-Ray
  • DNA-Binding Proteins
  • Escherichia coli Proteins*
  • Evolution, Molecular
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / chemistry*
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins / chemistry
  • Heat-Shock Proteins / metabolism
  • Humans
  • Hydrolysis
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Isoforms
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Transcription Factors


  • BCL2-associated athanogene 1 protein
  • Bacterial Proteins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Escherichia coli Proteins
  • GrpE protein, Bacteria
  • HSC70 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA8 protein, human
  • Heat-Shock Proteins
  • Protein Isoforms
  • Transcription Factors
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Adenosine Triphosphatases
  • dnaK protein, E coli

Associated data

  • PDB/1HX1