4.6 Article

A novel and unique ATP hydrolysis to AMP by a human Hsp70 Binding immunoglobin protein (BiP)

期刊

PROTEIN SCIENCE
卷 31, 期 4, 页码 797-810

出版社

WILEY
DOI: 10.1002/pro.4267

关键词

ADP; AMP; ATP; ATPase; BiP; heat shock proteins (HSPs); Hsp70; molecular chaperones; protein folding

资金

  1. American Heart Association [17GRNT33660506]
  2. Center for Strategic Scientific Initiatives, National Cancer Institute [R01CA229812]
  3. Division of Intramural Research, National Institute of Allergy and Infectious Diseases [R21AI140006]
  4. National Institute of General Medical Sciences [R01GM098592]
  5. Virginia Commonwealth University

向作者/读者索取更多资源

Hsp70s are important molecular chaperones that play crucial roles in maintaining cellular protein homeostasis. Among them, BiP in the endoplasmic reticulum exhibits a unique ATP hydrolysis to AMP activity, distinct from the canonical ATP to ADP hydrolysis observed in other Hsp70 proteins. This novel finding may provide new insights into the activity and cellular function of BiP.
Hsp70s are ubiquitous and highly conserved molecular chaperones. They play crucial roles in maintaining cellular protein homeostasis. It is well established that Hsp70s use the energy of ATP hydrolysis to ADP to power the chaperone activity regardless of the cellular locations and isoforms. Binding immunoglobin protein (BiP), the major member of Hsp70s in the endoplasmic reticulum, is essential for protein folding and quality control. Unexpectedly, our structural analysis of BiP demonstrated a novel ATP hydrolysis to AMP during crystallization under the acidic conditions. Our biochemical studies confirmed this newly discovered ATP to AMP hydrolysis in solutions. Unlike the canonical ATP to ADP hydrolysis observed for Hsp70s, this ATP hydrolysis to AMP depends on the substrate-binding domain of BiP and is inhibited by the binding of a peptide substrate. Intriguingly, this ATP to AMP hydrolysis is unique to BiP, not shared by two representative Hsp70 proteins from the cytosol. Taken together, this novel and unique ATP to AMP hydrolysis may provide a potentially new direction for understanding the activity and cellular function of BiP.

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