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

Author(s)

Dores-Silva, P. R. ^[1] ; Minari, K. ^{[1, 2]} ; Ramos, C. H. I. ^[3] ; Barbosa, L. R. S. ^[4] ; Borges, J. C. ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Fed Sao Carlos, Ctr Ciencias Biol & Saude, BR-13565905 Sao Carlos, SP - Brazil

^[3] Univ Estadual Campinas, Inst Quim, UNICAMP, BR-13083970 Campinas, SP - Brazil

^[4] Univ Sao Paulo, Inst Fis, Dept Fis Geral, Grp Biofis, BR-05508090 Sao Paulo - Brazil

• Document type: Journal article
• Source: International Journal of Biological Macromolecules; v. 56, p. 140-148, MAY 2013.
• Web of Science Citations: 11

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 hHepl oligomerizes in a concentration-dependent fashion and that the zinc ion, which is essential for hHepl in vivo function, has an important protein-structure stabilizing effect. (C) 2013 Elsevier B.V. All rights reserved. (AU)