title: Structural and stability studies of the human mtHsp70-escort protein 1: an essential mortalin co-chaperone.
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.
authors: Instituto de Química de São Carlos, Universidade de São Paulo - USP, São Carlos, SP 13560-970, Brazil.
authors: P R
authors: PR
authors: Dores-Silva
authors: K
authors: K
authors: Minari
authors: C H I
authors: CH
authors: Ramos
authors: L R S
authors: LR
authors: Barbosa
authors: J C
authors: JC
authors: Borges
mesh_terms: D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D057446:Hydrodynamics; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D017510:Protein Folding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000378:metabolism; D015032:Zinc / Q000494:pharmacology; D016335:Zinc Fingers
chemical_list: C559905:DNLZ protein, human; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D011994:Recombinant Proteins; C080352:mortalin; D014364:Tryptophan; D015032:Zinc