Identification and characterization of a human mitochondrial homologue of the bacterial co-chaperone GrpE

Gene
A A ChoglayM E Cheetham

Abstract

We have identified a novel human cDNA with a predicted protein sequence that has 28% amino acid identity with the E. coli Hsp70 co-chaperone GrpE and designated it HMGE. Even with this low level of amino acid identity the human sequence could be efficiently modelled on the X-ray structure of the E. coli protein, suggesting that there may be significant functional conservation. Indeed, HMGE expressed in E. coli as a GST fusion protein co-purified with the E. coli Hsp70 protein DnaK in the absence of ATP. DnaK could be released from the GST-HMGE with a Mg-ATP wash. Subcellular fractionation and immunocytochemistry studies using antisera raized against HMGE show that it is a mitochondrial protein. In contrast to studies of rat GrpE, however, HMGE also appears to bind the constitutive cytosolic Hsp70, Hsc70, in addition to mitochondrial Hsp70, Mt-Hsp70. We have previously shown that Hsc70 nucleotide-exchange is rate limiting in the presence of the DnaJ-protein, HSJ1b. However, HMGE was found to inhibit the HSJ1b-enhanced Hsc70 ATPase activity and may mediate this inhibition by binding the DnaJ-protein, HSJ1b. This is the first description of a direct interaction between a DnaJ protein and GrpE-like protein. These studies suggest th...Continue Reading

References

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Citations

Apr 16, 2010·The Journal of Biological Chemistry·Arvind Vittal GoswamiPatrick D'Silva
May 9, 2012·The Journal of Biological Chemistry·Jumpei MurakamiShigetada Kawabata
Jul 5, 2006·Cell Stress & Chaperones·Custer C DeocarisRenu Wadhwa
Apr 2, 2014·Protein Science : a Publication of the Protein Society·Joseph AmickSaurav Misra
Feb 16, 2007·Biochimica Et Biophysica Acta·James A MacKenzie, R Mark Payne
Feb 20, 2020·Biological Chemistry·Sylvie CallegariPeter Rehling
Jul 4, 2003·The Journal of Biological Chemistry·Júlio C BorgesCarlos H I Ramos
Dec 24, 2020·International Journal of Molecular Sciences·Peter NguyenNikolas Nikolaidis
Nov 21, 2019·Journal of Proteome Research·Petra S J RylJuri Rappsilber

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