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Description
Molecular chaperones are proteins with functions related to folding processes in the cell, such as correcting misfolding of client proteins, aggregation prevention and solubilization of aggregates. Human Hsp70-escort protein 1 (hHep1, or Zim17/TIM15/DNLZ) is a co-chaperone protein necessary for the activity of an essential chaperone in the cell: the mitochondrial Hsp70 (mtHsp70), which aids in refolding client proteins but highly unstable in the absence of hHep1 [1]. mtHsp70 also acts on membrane transport through the membrane, so hHep1 acts on these two central phenomena in the cell, but it is still not clear if hHep1 is needed for membrane transport just by preventing mtHsp70 self-aggregation or if it interacts with the membrane directly [2].
Recent works have shown evidence of the interaction of these proteins with liposomes, but little information is known regarding how these processes occur [3,4]. In this work, we have employed Small-Angle X-Ray Scattering (SAXS) for studying the interaction of hHep1 with negatively charged liposomes of different compositions (made of POPS and cardiolipin). Our results indicate that hHep1 docks onto the liposomes but does not penetrate considerably into the lipid membrane. This suggests that hHep1 has a more cooperative interaction with mtHsp70 for protein import through the membrane, which may occur by forming a complex or just by acting on mtHsp70, which then would act on the membrane.
[1] Sichting, M. et al. Maintenance of structure and function of mitochondrial Hsp70 chaperones requires the chaperone Hep1. EMBO J., v. 24, n. 5, p. 1046-1056 (2005)
[2] Bohnert, M., Pfanner, N., van der Laan, M. A dynamic machinery for import of mitochondrial precursor proteins. FEBS Lett., v. 581, n. 15, p. 2802-2810 (2007)
[3] Dores-Silva, P. R. et al. Human HSPA9 (mtHsp70, mortalin) interacts with lipid bilayers containing cardiolipin, a major component of the inner mitochondrial membrane. Biochim. Biophys. Acta - Biomembr., v. 1862, n. 11, p. 183436 (2020)
[4] Dores-Silva, P. R. et al. New insights on human Hsp70-escort protein 1: Chaperone activity, interaction with liposomes, cellular localizations and HSPA's self-assemblies remodeling. Int. J. Biol. Macromol., v. 182, p. 772-784 (2021)