The 70-Kilodalton Heat Shock Cognate Can Act as a Molecular Chaperone during the Membrane Translocation of a Plant Secretory Protein Precursor

1992 ◽  
Vol 4 (7) ◽  
pp. 821 ◽  
Author(s):  
Jan A. Miernyk ◽  
Nicholas B. Duck ◽  
Robert G. Shatters ◽  
William R. Folk
Keyword(s):  
Heat Shock ◽  
Molecular Chaperone ◽  
Secretory Protein ◽  
Membrane Translocation ◽  
Protein Precursor

scholarly journals Presequence and mature part of preproteins strongly influence the dependence of mitochondrial protein import on heat shock protein 70 in the matrix.

1993 ◽  
Vol 123 (1) ◽  
pp. 119-126 ◽  
Author(s):  
W Voos ◽  
B D Gambill ◽  
B Guiard ◽  
N Pfanner ◽  
E A Craig
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Fusion Protein ◽  
Fusion Proteins ◽  
Dual Role ◽  
Intermembrane Space ◽  
Heme Binding ◽  
Membrane Translocation ◽  
Amino Terminal ◽  
The Matrix

To test the hypothesis that 70-kD mitochondrial heat shock protein (mt-hsp70) has a dual role in membrane translocation of preproteins we screened preproteins in an attempt to find examples which required either only the unfoldase or only the translocase function of mt-hsp70. We found that a series of fusion proteins containing amino-terminal portions of the intermembrane space protein cytochrome b2 (cyt. b2) fused to dihydrofolate reductase (DHFR) were differentially imported into mitochondria containing mutant hsp70s. A fusion protein between the amino-terminal 167 residues of the precursor of cyt. b2 and DHFR was efficiently transported into mitochondria independently of both hsp70 functions. When the length of the cyt. b2 portion was increased and included the heme binding domain, the fusion protein became dependent on the unfoldase function of mt-hsp70, presumably caused by a conformational restriction of the heme-bound preprotein. In the absence of heme the noncovalent heme binding domain in the longer fusion proteins no longer conferred a dependence on the unfoldase function. When the cyt. b2 portion of the fusion protein was less than 167 residues, its import was still independent of mt-hsp70 function; however, deletion of the intermembrane space sorting signal resulted in preproteins that ended up in the matrix of wild-type mitochondria and whose translocation was strictly dependent on the translocase function of mt-hsp70. These findings provide strong evidence for a dual role of mt-hsp70 in membrane translocation and indicate that preproteins with an intermembrane space sorting signal can be correctly imported even in mutants with severely impaired hsp70 function.

scholarly journals The Effect of Oxidized Dopamine on the Structure and Molecular Chaperone Function of the Small Heat-Shock Proteins, αB-Crystallin and Hsp27

2021 ◽  
Vol 22 (7) ◽  
pp. 3700
Author(s):  
Junna Hayashi ◽  
Jennifer Ton ◽  
Sparsh Negi ◽  
Daniel E. K. M. Stephens ◽  
Dean L. Pountney ◽  
...  
Keyword(s):  
Heat Shock ◽  
Protein Aggregation ◽  
Molecular Chaperone ◽  
Cross Linking ◽  
Αb Crystallin ◽  
The Cross ◽  
Shock Proteins ◽  
And Function

Oxidation of the neurotransmitter, dopamine (DA), is a pathological hallmark of Parkinson’s disease (PD). Oxidized DA forms adducts with proteins which can alter their functionality. αB-crystallin and Hsp27 are intracellular, small heat-shock molecular chaperone proteins (sHsps) which form the first line of defense to prevent protein aggregation under conditions of cellular stress. In vitro, the effects of oxidized DA on the structure and function of αB-crystallin and Hsp27 were investigated. Oxidized DA promoted the cross-linking of αB-crystallin and Hsp27 to form well-defined dimer, trimer, tetramer, etc., species, as monitored by SDS-PAGE. Lysine residues were involved in the cross-links. The secondary structure of the sHsps was not altered significantly upon cross-linking with oxidized DA but their oligomeric size was increased. When modified with a molar equivalent of DA, sHsp chaperone functionality was largely retained in preventing both amorphous and amyloid fibrillar aggregation, including fibril formation of mutant (A53T) α-synuclein, a protein whose aggregation is associated with autosomal PD. In the main, higher levels of sHsp modification with DA led to a reduction in chaperone effectiveness. In vivo, DA is sequestered into acidic vesicles to prevent its oxidation and, intracellularly, oxidation is minimized by mM levels of the antioxidant, glutathione. In vitro, acidic pH and glutathione prevented the formation of oxidized DA-induced cross-linking of the sHsps. Oxidized DA-modified αB-crystallin and Hsp27 were not cytotoxic. In a cellular context, retention of significant chaperone functionality by mildly oxidized DA-modified sHsps would contribute to proteostasis by preventing protein aggregation (particularly of α-synuclein) that is associated with PD.

HSP70 and lysosomal storage disorders: novel therapeutic opportunities

2010 ◽  
Vol 38 (6) ◽  
pp. 1479-1483 ◽  
Author(s):  
Nikolaj H.T. Petersen ◽  
Thomas Kirkegaard
Keyword(s):  
Heat Shock ◽  
Stress Responses ◽  
Molecular Chaperone ◽  
Heat Shock Protein 70 ◽  
Physiological Stress ◽  
Lysosomal Storage ◽  
Catabolic Enzymes ◽  
Chaperone Hsp70 ◽  
Storage Disorders ◽  
Novel Therapeutic

Lysosomes, with their arsenal of catabolic enzymes and crucial metabolic housekeeping functions are experiencing a revived research interest after having lived a rather quiet life for the last few decades. With the discovery of the interaction of the lysosomes with another ancient component of cellular homoeostasis, the molecular chaperone HSP70 (heat-shock protein 70), the stage seems set for further discoveries of the mechanisms regulating cellular and physiological stress responses to otherwise detrimental challenges.

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