The hsp70 chaperone DnaK is a secondary amide peptide bond cis-trans isomerase

Schiene‐Fischer, Cordelia; Habazettl, Judith; Schmid, Franz X.; Fischer, Gunter

doi:10.1038/nsb804

Cited by 83 publications

(82 citation statements)

References 32 publications

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“…Surprisingly, in the full-length, lipomodified PrsA, the active site mutations did not disturb the catalysis of proline-limited folding in vitro, suggesting that PrsA also facilitates protein folding by some other mechanism than catalyzing the cis/trans isomerization of prolyl peptide bonds. It has recently been shown that the DnaK chaperone catalyzes the cis/trans isomerization of nonprolyl peptide bonds (43). The difference of activity between soluble and lipomodified mutant proteins may reside in the pattern of multimerization or protein-protein association of PrsA monomers.…”

Section: Discussionmentioning

confidence: 99%

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Vitikainen

Lappalainen

Seppälä

et al. 2004

Journal of Biological Chemistry

118

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The PrsA protein of Bacillus subtilis is an essential membrane-bound lipoprotein that is assumed to assist post-translocational folding of exported proteins and stabilize them in the compartment between the cytoplasmic membrane and cell wall. This folding activity is consistent with the homology of a segment of PrsA with parvulin-type peptidyl-prolyl cis/trans isomerases (PPIase). In this study, molecular modeling showed that the parvulin-like region can adopt a parvulin-type fold with structurally conserved active site residues. PrsA exhibits PPIase activity in a manner dependent on the parvulin-like domain. We constructed deletion, peptide insertion, and amino acid substitution mutations and demonstrated that the parvulin-like domain as well as flanking N-and C-terminal domains are essential for in vivo PrsA function in protein secretion and growth. Surprisingly, none of the predicted active site residues of the parvulin-like domain was essential for growth and protein secretion, although several active site mutations reduced or abolished the PPIase activity or the ability of PrsA to catalyze proline-limited protein folding in vitro. Our results indicate that PrsA is a PPIase, but the essential role in vivo seems to depend on some non-PPIase activity of both the parvulin-like and flanking domains.

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Section: Discussionmentioning

confidence: 99%

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Vitikainen

Lappalainen

Seppälä

et al. 2004

Journal of Biological Chemistry

118

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“…The bacterial Hsp70 DnaK was shown to catalyze this so-called APIase reaction (for amide peptide bond cistrans isomerase), but it is unknown whether this is a general activity of Hsp70 proteins (Schiene-Fischer et al 2002).…”

Section: Ppismentioning

confidence: 99%

Protein Folding in the Endoplasmic Reticulum

Braakman

Hebert

2013

Cold Spring Harbor Perspectives in Biology

430

349

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In this article, we will cover the folding of proteins in the lumen of the endoplasmic reticulum (ER), including the role of three types of covalent modifications: signal peptide removal, Nlinked glycosylation, and disulfide bond formation, as well as the function and importance of resident ER folding factors. These folding factors consist of classical chaperones and their cochaperones, the carbohydrate-binding chaperones, and the folding catalysts of the PDI and proline cis -trans isomerase families. We will conclude with the perspective of the folding protein: a comparison of characteristics and folding and exit rates for proteins that travel through the ER as clients of the ER machinery.

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“…The disaggregation mechanism involves a sequential action, first of ClpB modifying the surface of large compact aggregates thus increasing DnaK affinity, and second, of DnaK binding and unfolding entangled polypeptides, which accelerates cis-trans isomerizations in secondary amide bonds of refolding polypeptides (12,13). The efficiency of chaperone-mediated disaggregation strongly depends on the nature of the protein, on the aggregate size, and its solubility (4,10,11).…”

mentioning

confidence: 99%

Proteinaceous Infectious Behavior in Non-pathogenic Proteins Is Controlled by Molecular Chaperones

Ben‐Zvi¹,

Goloubinoff²

2002

Journal of Biological Chemistry

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External stresses or mutations may cause labile proteins to lose their distinct native conformations and seek alternatively stable aggregated forms. Molecular chaperones that specifically act on protein aggregates were used here as a tool to address the biochemical nature of stable homo-and hetero-aggregates from nonpathogenic proteins formed by heat-stress. Confirmed by sedimentation and activity measurements, chaperones demonstrated that a single polypeptide chain can form different species of aggregates, depending on the denaturing conditions. Indicative of a cascade reaction, sub-stoichiometric amounts of one fast-aggregating protein strongly accelerated the conversion of another soluble, slow-aggregating protein into insoluble, chaperone-resistant aggregates. Chaperones strongly inhibited seed-induced protein aggregation, suggesting that they can prevent and cure proteinaceous infectious behavior in homo-and hetero-aggregates from common and disease-associated proteins in the cell.

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The hsp70 chaperone DnaK is a secondary amide peptide bond cis-trans isomerase

Cited by 83 publications

References 32 publications

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Structure-Function Analysis of PrsA Reveals Roles for the Parvulin-like and Flanking N- and C-terminal Domains in Protein Folding and Secretion in Bacillus subtilis

Protein Folding in the Endoplasmic Reticulum

Proteinaceous Infectious Behavior in Non-pathogenic Proteins Is Controlled by Molecular Chaperones

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