The Large Hsp70 Grp170 Binds to Unfolded Protein Substrates in Vivo with a Regulation Distinct from Conventional Hsp70s

Abstract

Background: Large Hsp70s are structurally similar to conventional Hsp70s but functionally less well understood. Results: The endoplasmic reticulum cognate Grp170 binds directly to substrates in vivo, which is modulated by structural elements characteristic for large Hsp70s. Conclusion: Grp170 serves as a nucleotide exchange factor and a chaperone. Significance: In addition to BiP another Hsp70 superfamily member fulfills ER chaperone functions.

Dimerization-dependent Folding Underlies Assembly Control of the Clonotypic αβT Cell Receptor Chains

“…In agreement with data published previously (10,34,35) we found both ␣ RK-ϾLL and ␤ K-ϾL to be BiP substrates (Fig. 3A).…”

“…The action of Cnx, however, seems to be limited to early stages of ␣␤TCR biogenesis (32) and is not essential for the correct assembly of ␣␤TCRs (33). Additionally, the ER Hsp70 orthologue BiP (10,34) and the ER lumenal large Hsp70 Grp170 (35) bind to TCR ␣ and ␤ chains. The precise role of these chaperones in TCR assembly and their binding sites within the clonotypic TCR chains have remained unclear.…”

Proteome analysis in the assessment of ageing

“…The observed decreases in the expression of chaperone proteins (PPIB/CyPB, DNAJ3/HSP40, HSPCA/HSP86, and HYOU1) may compromise intracellular protein trafficking and increase cellular stress due to elevated protein misfolding (Behnke and Hendershot, 2014;Proctor et al, 2005) and perturbed removal of misfolded proteins (Merker and Grune, 2000). Thereby the increased expression of T-kininogen, an inhibitor of cysteine proteinases (Greenbaum et al, 1992), may be a contributing factor.…”

A novel nanoparticle containing neuritin peptide with grp170 induces a CTL response to inhibit tumor growth

“…Grp170 is a major molecular chaperone of the HSP family that is primarily located in the endoplasmic reticulum and induced by stress conditions such as hypoxia, ischemia, and disruption of calcium homeostasis [11][12][13]. In addition, the stress protein grp170 can function as a highly efficient molecular chaperone, binding to large protein substrates and acting as a potent vaccine against specific tumors [14][15][16].…”