Structural and stability studies of the human mtHsp70-escort protein 1: An essential mortalin co-chaperone

https://doi.org/10.1016/j.ijbiomac.2013.02.009Get rights and content
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Abstract

Mitochondrial Hsp70 is involved in both protein import and folding process, among other essential functions. In mammalian cells, due to its role in the malignant process, it receives the name of mortalin. Despite its importance in protein and mitochondrial homeostasis, mortalin tends to self-aggregate in vitro and in vivo, the later leads to mitochondrial biogenesis failure. Recently, a zinc-finger protein, named Hsp70-escort protein 1 (Hep1, also called Zim17/TIM15/DNLZ), was described as an essential human mitochondrial mortalin co-chaperone which avoids its self-aggregation. Here, we report structural studies of the human Hep1 (hHep1). The results indicate that hHep1 shares some structural similarities with the yeast ortholog despite the low identity and functional differences. We also observed that hHep1 oligomerizes in a concentration-dependent fashion and that the zinc ion, which is essential for hHep1 in vivo function, has an important protein-structure stabilizing effect.

Abbreviations

AUC
analytical ultracentrifugation
CD
circular dichroism
DSC
differential scanning calorimetry
f/f0
frictional ratio
MM
molecular mass
Rs
Stokes radius
Rg
radius of gyration
SAXS
small angle X-ray scattering
s20,w
sedimentation coefficient at standard conditions
s020,w
standard sedimentation coefficient at 0 mg mL−1 of protein
[Θ]
residual molar ellipticity
λ
spectral center of mass

Keywords

Hep1
mtHsp70
Mortalin
Fluorescence
Analytical ultracentrifugation
Oligomerization

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