Inhibition of Hsp70 ATPase activity and protein renaturation by a novel Hsp70-binding protein

Deborah A. Raynes, Vince Guerriero

Research output: Contribution to journalArticlepeer-review

99 Scopus citations


A cDNA that codes for an Hsp70-interacting protein (HspBP1) was isolated from a human heart cDNA library using the yeast two-hybrid system. The derived amino acid sequence is unique and therefore represents a new regulator of Hsp70. Northern blots of RNA from human tissues indicate that HspBP1 mRNA has a size of approximately 1.7 kilobase pairs and is present in all tissues analyzed but is most abundant in heart and skeletal muscle. Western blot analysis revealed a protein of approximately 40 kilodaltons detected in cell extracts. The ATPase domain of Hsp70 demonstrated binding to HspBP1. Further experiments showed binding of HspBP1 to Hsp70 and Hse70 in a total heart extract. HspBP1 (8 μM) inhibited approximately 90% of the Hsp40- activated Hsp70 ATPase activity. HspBP1 prevented ATP binding to Hsp70, and therefore this is the likely mechanism of inhibition. Hsp40-activated ATPase activity is essential for the renaturation activity of Hsp70; therefore, the effects of HspBP1 on renaturation of luciferase in a reticulocyte lysate and a defined system were examined. HspBP1 inhibited renaturation with half- maximal inhibition at 2 μM. These data indicate that we have identified a novel Hsp70-interacting protein that inhibits Hsp70 chaperone activity.

Original languageEnglish (US)
Pages (from-to)32883-32888
Number of pages6
JournalJournal of Biological Chemistry
Issue number49
StatePublished - Dec 4 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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