Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK
The role of bacterial Hsp40, DnaJ, is to co-chaperone the binding of misfolded or alternatively folded proteins to bacterial Hsp70, DnaK, which is an ATP-fuelled unfolding chaperone. In addition to its DnaK targeting activity, DnaJ has a weak thiol-reductase activity. In between the substrate-bindin...
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doaj-902b48ae441b4147bfdb4d03aabe5eb32020-11-24T20:51:24ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2014-07-01110.3389/fmolb.2014.00007102289Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaKRayees Ul Hassan Mattoo0America eFarina Henriquez Cuendet1Subbanna eSujatha2Andrija eFinka3Smriti ePriya4Sandeep Kumar Sharma5Pierre eGoloubinoff6University of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneUniversity of LausanneThe role of bacterial Hsp40, DnaJ, is to co-chaperone the binding of misfolded or alternatively folded proteins to bacterial Hsp70, DnaK, which is an ATP-fuelled unfolding chaperone. In addition to its DnaK targeting activity, DnaJ has a weak thiol-reductase activity. In between the substrate-binding domain and the J-domain anchor to DnaK, DnaJ has a unique domain with four conserved CXXC motives that bind two Zn2+ and partly contribute to polypeptide binding. Here, we deleted in DnaJ this Zn-binding domain, which is characteristic to type I but not of type II or III J-proteins. This caused a loss of the thiol-reductase activity and strongly reduced the ability of DnaJ to mediate the ATP- and DnaK-dependent unfolding/refolding of mildly oxidized misfolded polypeptides, an inhibition that was alleviated in the presence of thioredoxin or DTT. We suggest that in addition to their general ability to target misfolded polypeptide substrates to the Hsp70/Hsp110 chaperone machinery, Type I J-proteins carry an ancillary protein dithiol-isomerase function that can synergize the unfolding action of the chaperone, in the particular case of substrates that are further stabilized by non-native disulfide bonds. Whereas the unfoldase can remain ineffective without the transient untying of disulfide bounds by the foldase, the foldase can remain ineffective without the transient ATP-fuelled unfolding of wrong local structures by the unfoldase.http://journal.frontiersin.org/Journal/10.3389/fmolb.2014.00007/fullThioredoxinsAggregationHsp70chaperonesprotein disulfide isomeraseDNAJ Homologues |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rayees Ul Hassan Mattoo America eFarina Henriquez Cuendet Subbanna eSujatha Andrija eFinka Smriti ePriya Sandeep Kumar Sharma Pierre eGoloubinoff |
spellingShingle |
Rayees Ul Hassan Mattoo America eFarina Henriquez Cuendet Subbanna eSujatha Andrija eFinka Smriti ePriya Sandeep Kumar Sharma Pierre eGoloubinoff Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK Frontiers in Molecular Biosciences Thioredoxins Aggregation Hsp70 chaperones protein disulfide isomerase DNAJ Homologues |
author_facet |
Rayees Ul Hassan Mattoo America eFarina Henriquez Cuendet Subbanna eSujatha Andrija eFinka Smriti ePriya Sandeep Kumar Sharma Pierre eGoloubinoff |
author_sort |
Rayees Ul Hassan Mattoo |
title |
Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK |
title_short |
Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK |
title_full |
Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK |
title_fullStr |
Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK |
title_full_unstemmed |
Synergism between a foldase and an unfoldase: Reciprocal dependence between the thioredoxin-like activity of DnaJ and the polypeptide-unfolding activity of DnaK |
title_sort |
synergism between a foldase and an unfoldase: reciprocal dependence between the thioredoxin-like activity of dnaj and the polypeptide-unfolding activity of dnak |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Biosciences |
issn |
2296-889X |
publishDate |
2014-07-01 |
description |
The role of bacterial Hsp40, DnaJ, is to co-chaperone the binding of misfolded or alternatively folded proteins to bacterial Hsp70, DnaK, which is an ATP-fuelled unfolding chaperone. In addition to its DnaK targeting activity, DnaJ has a weak thiol-reductase activity. In between the substrate-binding domain and the J-domain anchor to DnaK, DnaJ has a unique domain with four conserved CXXC motives that bind two Zn2+ and partly contribute to polypeptide binding. Here, we deleted in DnaJ this Zn-binding domain, which is characteristic to type I but not of type II or III J-proteins. This caused a loss of the thiol-reductase activity and strongly reduced the ability of DnaJ to mediate the ATP- and DnaK-dependent unfolding/refolding of mildly oxidized misfolded polypeptides, an inhibition that was alleviated in the presence of thioredoxin or DTT. We suggest that in addition to their general ability to target misfolded polypeptide substrates to the Hsp70/Hsp110 chaperone machinery, Type I J-proteins carry an ancillary protein dithiol-isomerase function that can synergize the unfolding action of the chaperone, in the particular case of substrates that are further stabilized by non-native disulfide bonds. Whereas the unfoldase can remain ineffective without the transient untying of disulfide bounds by the foldase, the foldase can remain ineffective without the transient ATP-fuelled unfolding of wrong local structures by the unfoldase. |
topic |
Thioredoxins Aggregation Hsp70 chaperones protein disulfide isomerase DNAJ Homologues |
url |
http://journal.frontiersin.org/Journal/10.3389/fmolb.2014.00007/full |
work_keys_str_mv |
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