Abstract
Human Hsp70-escort protein 1 (hHep1) is a cochaperone that assists in the function and stability of mitochondrial HSPA9. Similar to HSPA9, hHep1 is located outside the mitochondria and can interact with liposomes. In this study, we further investigated the structural and thermodynamic behavior of interactions between hHep1 and negatively charged liposomes, as well as interactions with cellular membranes. Our results showed that hHep1 interacts peripherally with liposomes formed by phosphatidylserine and cardiolipin and remains partially structured, exhibiting similar affinities for both. In addition, after being added to the cell membrane, recombinant hHep1 was incorporated by cells in a dose-dependent manner. Interestingly, the association of HSPA9 with hHep1 improved the incorporation of these proteins into the lipid bilayer. These results demonstrated that hHep1 can interact with lipids also present in the plasma membrane, indicating roles for this cochaperone outside of mitochondria.
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Acknowledgements
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) grants (#2012/50161-8, #2014/16646-0, #2016/22477-1, #2017/07335-9, #2017/26131-5, #2019/22422-0 and #2021/12775-3), by the Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) grant (grant #303262/2018-4 and #310927/2021-8), by the National Institutes of Health (NIH) grants: R01 GM098455-04 and R01 GM114473-01, by MUR (Departments of excellence 2018-2022; E91I18001480001) and the University of Modena and Reggio Emilia (Unimore FAR2020 Mission Oriented).
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Moritz, M.N.O., Dores-Silva, P.R., Coto, A.L.S. et al. Human HSP70-escort protein 1 (hHep1) interacts with negatively charged lipid bilayers and cell membranes. Cell Stress and Chaperones 28, 1001–1012 (2023). https://doi.org/10.1007/s12192-023-01394-1
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DOI: https://doi.org/10.1007/s12192-023-01394-1