The DNLZ/HEP zinc‐binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9

Vu, Michael; Zhai, Peng; Lee, Juhye; Guerra, Cecília; Liu, Shirley; Gustin, Michael C.; Silberg, Jonathan J.

doi:10.1002/pro.2012

Cited by 18 publications

(15 citation statements)

References 47 publications

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“…Studies using new conditional mutants of Zim17 demonstrated that the observed loss of respiratory activity is most likely due to a functional defect of Fe/S cluster synthesis by Ssq1 while a defective protein translocation system is caused by a prolonged substrate interaction of Ssc1 [41]. Similar observations of a direct regulation of mtHsp70 activity have also been obtained in the mammalian system [42]. In this context, it was hypothesized that the zinc-binding domain of Zim17 complements the activity that is provided by the J-domain protein Pam18, which lacks the equivalent of a C-terminal zinc-finger domain found in standard DnaJ homologs [43].…”

Section: Hsp70supporting

confidence: 58%

Chaperones and Proteases of Mitochondria: From Protein Folding and Degradation to Mitophagy

Voos¹,

Rüb²,

Bruderek³

2014

The Molecular Chaperones Interaction Networks in Protein Folding and Degradation

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In eukaryotic cells, mitochondria fulfill a multitude of essential functions. Under both normal and stress conditions, a complex system of molecular chaperones and protease enzymes is at work to maintain mitochondrial biogenesis and protein quality control (PQC), summarized as "mitochondrial protein homeostasis." Mitochondrial chaperones of the heat shock protein Hsp60 and Hsp70 families play main roles in the import and folding of nuclear-encoded polypeptides, representing the majority of the mitochondrial proteome. These enzymes together with chaperones of the Clp family prevent the accumulation of aggregated or superfluous polypeptides in a close cooperation with specific PQC proteases of the AAA+ (adenosine triphosphatases associated with diverse cellular activities) family. Recent evidence demonstrated the removal of terminally damaged mitochondria as a whole by a variation of autophagy, termed mitophagy, as an additional level of mitochondrial quality control. The details of mitochondrial protein homeostasis, comprising the functional contribution of this broad set of chaperones and proteases will be discussed here.

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Section: Hsp70supporting

confidence: 58%

Chaperones and Proteases of Mitochondria: From Protein Folding and Degradation to Mitophagy

Voos¹,

Rüb²,

Bruderek³

2014

The Molecular Chaperones Interaction Networks in Protein Folding and Degradation

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“…Phylogenetic data suggest that ZR, HEP2, and HEP proteins are related to each other and form a common family of organellar proteins, although the sequence similarities between the five subgroups of the family are rather low. A presumed functional conservation of the family members is supported by full complementation of yeast hep1 mutant strains with ZR3 from Arabidopsis (this study), and partial complementation with human HEP/DNLZ, respectively [8,14]. Additionally, HEP1 from yeast, ZR3 from Arabidopsis, HEP from human, and plastidial HEP2 from C. reinhardtii were demonstrated to interact biochemically with the respective organellar Hsp70 chaperones [12,15,16,20], and this study].…”

Section: Discussionmentioning

confidence: 77%

Arabidopsis Zinc Ribbon 3 is the ortholog of yeast mitochondrial HSP70 escort protein HEP1 and belongs to an ancient protein family in mitochondria and plastids

et al. 2012

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Edited by Ulf-Ingo FluggeKeywords: Mitochondria Protein import Chaperone HSP ETCHED1 ZIM17/TIM15 a b s t r a c t ZR proteins belong to a phylogenetically conserved family of small zinc-ribbon proteins in plastids and mitochondria of higher plants. The function of these proteins is so far unclear. The mitochondrial proteins share sequence similarities with mitochondrial Hsp70 escort proteins (HEP) from Saccharomyces cerevisiae (HEP1) and human. Expression of the mitochondrial ZR protein from Arabidopsis, ZR3, rescued a hep1 knockout mutant from yeast. Accordingly, ZR3 was found to physically interact with mitochondrial Hsp70 from Arabidopsis. Our findings support the idea that mitochondrial and plastidic ZR proteins from higher plants are orthologs of HEP proteins. Structured summary of protein interactions:ZR3 physically interacts with mtHSC70-2 by pull down (View interaction) ZR3 physically interacts with mtHSC70-1 by pull down (View interaction)

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“…This small protein has a zinc-finger motif formed by four cysteines in a conserved zinc-finger domain (ZFD) almost 100 amino acids long (Fig. 1) (Momose et al 2007;Vu et al 2012;Yamamoto et al 2005).…”

Section: Hip: a Highly Elongated Hsp70 Co-chaperonementioning

confidence: 99%

A review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering

et al. 2016

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Intrinsic flexibility is closely related to protein function, and a plethora of important regulatory proteins have been found to be flexible, multi-domain or even intrinsically disordered. On the one hand, understanding such systems depends on how these proteins behave in solution. On the other, small-angle X-ray scattering (SAXS) is a technique that fulfills the requirements to study protein structure and dynamics relatively quickly with few experimental limitations. Molecular chaperones from Hsp70 and Hsp90 families are multi-domain proteins containing flexible and/or disordered regions that play central roles in cellular proteostasis. Here, we review the structure and function of these proteins by SAXS. Our general approach includes the use of SAXS data to determine size and shape parameters, as well as protein shape reconstruction and their validation by using accessory biophysical tools. Some remarkable examples are presented that exemplify the potential of the SAXS technique. Protein structure can be determined in solution even at limiting protein concentrations (for example, human mortalin, a mitochondrial Hsp70 chaperone). The protein organization, flexibility and function (for example, the J-protein co-chaperones), oligomeric status, domain organization, and flexibility (for the Hsp90 chaperone and the Hip and Hep1 co-chaperones) may also be determined. Lastly, the shape, structural conservation, and protein dynamics (for the Hsp90 chaperone and both p23 and Aha1 co-chaperones) may be studied by SAXS. We believe this review will enhance the application of the SAXS technique to the study of the molecular chaperones.

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The DNLZ/HEP zinc‐binding subdomain is critical for regulation of the mitochondrial chaperone HSPA9

Cited by 18 publications

References 47 publications

Chaperones and Proteases of Mitochondria: From Protein Folding and Degradation to Mitophagy

Chaperones and Proteases of Mitochondria: From Protein Folding and Degradation to Mitophagy

Arabidopsis Zinc Ribbon 3 is the ortholog of yeast mitochondrial HSP70 escort protein HEP1 and belongs to an ancient protein family in mitochondria and plastids

A review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering

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