The yeast Hsp110, Sse1p, exhibits high‐affinity peptide binding

Abstract

Hsp110s are divergent relatives of Hsp70 chaperones that hydrolyze ATP. Hsp110s serve as Hsp70 nucleotide exchange factors and act directly to maintain polypeptide solubility. To date, the impact of peptide binding on Hsp110 ATPase activity is unknown and an Hsp110/peptide affinity has not been measured. We now report on a peptide that binds to the yeast Hsp110, Sse1p, with a K D of $2 nM. Surprisingly, the binding of this peptide fails to stimulate Sse1p ATP hydrolysis. Moreover, an Hsp70-binding peptide is unable to associate with Sse1p, suggesting that Hsp70s and Hsp110s possess partially distinct peptide recognition motifs.

Heat shock protein 110 improves the anti-tumor effects of the cytotoxic T lymphocyte epitope E7 in mice

“…22,23,[58][59][60] Among HSPs, HSP110 exhibits higher binding affinity with proteins when compared to the HSP70s family. 39,40,47,48,56,61 Consequently, a potent immune response was generated by the addition of HSP110, as observed in our studies.…”

“…29,[37][38][39] In contrast to HSP70, the peptide-specific chaperon properties of HSP110 remain largely uncharacterized. 40 Goeckeler et al reported that yeast HSP110 exhibited high-affinity binding in vitro with peptide derived from the precursor of chicken mitochondrial aspartate aminotransferase, suggesting Hsp110 may be highly effective in anti-cancer peptide-based vaccines. 40 In this study, we combined the extensively studied HPV16 E7 [49][50][51][52][53][54][55][56][57] (RAHYNIVTF) CTL epitope [41][42][43][44][45] with the high-affinity peptide binding chaperone property of mouse HSP110 to improve antigen peptide presentation, generate HPV16 E7 [49][50][51][52][53][54][55][56][57] specific CTL response and enhance the anti-tumor ability in a cervical cancer murine model.…”

“…19,[25][26][27][28] Among the HSPs, HSP110 has a much higher protein binding affinity than the HSP70s family. 39,40,[46][47][48] However, whether HSP110 can enhance the immunogenicity of epitope peptide remained unclear. Accordingly, in this study we investigated the efficacy of the mHSP110 molecular chaperone as an immunoadjuvant to enhance the immunogenicity of the HPV16 E7 49-57 peptide vaccine.…”

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

“…In the ER, where BiP is the only ER Hsp70 family member, this is a possibility, but in the cytosol, which contains multiple constitutive and inducible Hsp70s and in some cases also possesses several large Hsp70s, this possibility is less appealing. Alternatively, it is possible that Grp170 and BiP bind to different sites on the same substrates or do not have completely overlapping substrates, as suggested by in vitro studies with large Hsp70s (42,43,47). Finally, the binding of Grp170 to proteins might signal a different fate for the substrate than when it is associated with BiP.…”

Hsp70 nucleotide exchange factor Fes1 is essential for ubiquitin-dependent degradation of misfolded cytosolic proteins

“…In contrast to Fes1, Hsp110 is a chaperone that recently has been shown to directly bind hydrophobic peptides (41)(42)(43). Thus, direct binding of hydrophobic patches might help to maintain the misfolded protein soluble, help the protein to fold, and shield it from interactions with the ubiquitylation machinery.…”