Hsp31, a member of the DJ-1 superfamily, is a multitasking stress responder with chaperone activity

Abstract

Among different types of protein aggregation, amyloids are a biochemically well characterized state of protein aggregation that are associated with a large number of neurodegenerative diseases including Parkinson's disease, Alzheimer and Creutzfeldt-Jakob disease. Yeast, Saccharomyces cerevisiae is an insightful model to understand the underlying mechanism of protein aggregation. Many yeast molecular chaperones can modulate aggregation and misfolding of proteins including α-Syn and the Sup35 prion. Hsp31 is a homodimeric protein structurally similar to human DJ-1, a Parkinson's disease-linked protein, and both are members of the DJ-1/ThiJ/PfpI superfamily. An emerging view is that Hsp31 and its associated superfamily members each have divergent multitasking functions that have the common theme of responding and managing various types of cellular stress. Hsp31 has several biochemical activities including chaperone and detoxifying enzyme activities that modulate at various points of a stress pathway such as toxicity associated with protein misfolding. However, we have shown the protective role of Hsp31's chaperone activity can operate independent of detoxifying enzyme activities in preventing the early stages of protein aggregate formation and associated cellular toxicities. We provide additional data that collectively supports the multiple functional roles that can be accomplished independent of each other. We present data indicating Hsp31 purified from yeast is more active compared to expression and purification from E. coli suggesting that posttranslational modifications could be important for Hsp31 to be fully active. We also compare the similarities and differences in activities among paralogs of Hsp31 supporting a model in which this protein family has overlapping but diverging roles in responding to various sources of cellular stresses.

The structure of the Pfp1 protease from the hyperthermophilic archaeonThermococcus thioreducensin two crystal forms

“…It has been noted that proteases of the Pfp1 family cross-react with antibodies against proteasomes (Snowden et al, 1992). The sequestration of active sites, here in complex tubes composed of multiple rings, has been noted as a feature of proteasomes, and other features have been remarked upon that are reminiscent of proteasomes (Aslam & Hazbun, 2016). The observation of clustered, complex proteolytic super-sites reported here may be an addition to this collection.…”

Oxidative stress triggers aggregation of GFP-tagged Hsp31p, the budding yeast environmental stress response chaperone, and glyoxalase III

“…S. cerevisiae HSP31 is a relatively recent addition to the list of stress-responsive genes. For years, this gene has received little interest except as a human DJ-1 orthologue, but it has recently been extensively studied in S. cerevisiae (Natkańska et al 2017 ; Aslam et al 2016 ; Aslam and Hazbun 2016 ; Bankapalli et al 2015 ; Amm et al 2015 ; Tsai et al 2015 ; Wilson 2014 ; Miller-Fleming et al 2014 ). HSP31 orthologues from related yeast species have also been investigated (Zhao et al 2014 ; Hasim et al 2014 ).…”

“…DJ-1 is by far the most frequently studied protein in this family. Nevertheless, the exact roles of DJ-1 in human cells (Chan and Chan 2015 ), Candida albicans Glx3, which belongs to the same family (Hasim et al 2014 ), and S. cerevisiae Hsp31p (Natkańska et al 2017 ; Aslam and Hazbun 2016 ) are not fully understood. One helpful clue for deciphering their biological role(s) is their cellular localization.…”

Características comunes de las chaperonas pequeñas y diméricas

“…Las Hsp31 son proteínas que van de los 25 a los 33 kDa. Pertenecen a la superfamilia de proteínas DJ-1/ThiJ/PfpI que están presentes en los tres dominios de la vida, siendo la proteína DJ-1 humana la más estudiada (Aslam & Hazbun, 2016;Lucas & Marín, 2007). Los miembros de la familia DJ-1 con actividad de chaperona se caracterizan por ser proteínas diméricas y se pueden clasificar según la forma en la que se unen los monómeros en el dímero (Jung et al, 2012;Wei, Ringe, Wilson & Ondrechen, 2007).…”