Functional characterization of natural variants found on the major stress inducible 70-kDa heat shock gene, HSPA1A, in humans.

ABSTRACT: In this report, we investigated the effects of natural single nucleotide polymorphisms on the function of HSPA1A, the major stress-inducible Hsp70 gene in humans. We first established that all mutant proteins retain their ability to hydrolyze ATP, but three of them had a significantly lower rate of ATP hydrolysis as compared to the wild-type (WT) protein. We also used Isothermal Titration Calorimetry and found that although all mutants bind to protein substrate with dissociation constants similar to the WT protein, four of them had increased reaction entropies. We also tested whether these mutations affect the ability of HSPA1A to refold heat-denatured luciferase. These assays revealed that one mutation resulted in significantly lower levels while a second one resulted in higher levels of

SUBMITTER: Oliverio R 

PROVIDER: S-EPMC6277039 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature