Modulation of the ATPase Cycle of BiP by Peptides and Proteins

Mayer, Marcus; Reinstein, Jochen; Büchner, Johannes

doi:10.1016/s0022-2836(03)00556-4

Cited by 45 publications

(36 citation statements)

References 50 publications

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“…Current knowledge suggests that PDI-D␤ proteins possess chaperone-like activities. Wind is required for export from the ER of an essential Golgi trans-membrane proteoglycan-modifying enzyme, Pipe (a 2-O-sulfotransferase), which otherwise remains trapped in the ER (8), and human and rat ERp29 (the human protein is also known as ERp28) interact with mutant hepatitis B surface antigen and thyroglobulin, respectively (17,18).…”

mentioning

confidence: 99%

Conserved Structural and Functional Properties of D-domain Containing Redox-active and -inactive Protein Disulfide Isomerase-related Protein Chaperones

Lippert

Diao

Barak

et al. 2007

Journal of Biological Chemistry

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The structure and mode of binding of the endoplasmic reticulum protein disulfide isomerase-related proteins to their substrates is currently a focus of intensive research. We have recently determined the crystal structure of the Drosophila melanogaster protein disulfide isomerase-related protein Within the endoplasmic reticulum (ER), 3 an optimal protein folding environment (1) essential for many secretory proteins is provided by a battery of ER chaperones and folding factors, including the chaperones calnexin/calreticulin (2), the Hsp70 homolog immunoglobulin heavy chain binding protein (BiP), and the protein disulfide isomerase (PDI)-related family of redox enzymes and chaperones (3, 4).PDI-related proteins have various functions (5), including redox and chaperone activities, regulation of calcium homeostasis, and regulation of protein export from the ER for degradation. Although relatively much is known about the respective mechanisms of chaperone action of the calnexin/calreticulin proteins and BiP (6 -9), less is known about the detailed molecular basis of PDI-chaperone activity. This is, to a significant extent, due to the weak character of PDI-substrate interactions. Thus, although it is now known that not only the chaperone function of these proteins but to varying extents their redox activity as well relies on their non-covalent interaction with substrate proteins (4, 10 -13), our knowledge of peptide specificity, peptide binding sites, or the molecular basis for the observed substrate selectivity of these proteins remains sketchy.Redox activity and chaperone function of PDI proteins requires interaction with substrates. The principle peptide binding site in PDI has been mapped to the bЈ-domain, although contributions from other domains occur (12). Thus, much attention has been focused on the redox-inactive domains. Recently, peptide binding sites in the b-domains of PDI, ERp57, and the ERp29 ortholog Wind have been described (14 -16). Interestingly, these binding sites all map to a region close to what would be the catalytically active redox-active sites in the a and aЈ domains of PDI.The first crystal structure of a complete PDI family member of the eukaryotic ER was determined in 2003 (13), allowing a direct structural interpretation of the peptide-binding sites. This Drosophila melanogaster protein, Wind, contains an N-terminal thioredoxin b-type domain found in most PDI-related proteins as well as a unique C-terminal domain (the D-domain) found only in the PDI-D group of PDI-related proteins (3).The PDI-D proteins comprise two subgroups. PDI-D␣ proteins contain one or more redox-active a-type thioredoxin domains, whereas only redox-inactive b-type domains are present in PDI-D␤ proteins. Current knowledge suggests that PDI-D␤ proteins possess chaperone-like activities. Wind is required for export from the ER of an essential Golgi trans-* This work was funded in part by the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and an Excellence Network of the State of Sachsen Anhalt. T...

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mentioning

confidence: 99%

Conserved Structural and Functional Properties of D-domain Containing Redox-active and -inactive Protein Disulfide Isomerase-related Protein Chaperones

Lippert

Diao

Barak

et al. 2007

Journal of Biological Chemistry

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“…activity and undergoes ATP-dependent conformational changes during folding. 47,48 Cells devoid of mtDNA are unable to generate ATP by oxidative phosphorylation and, as a result, experience metabolic stress that can influence protein expression in ER. 49 Interestingly, a previous study showed that the expression of chaperones like BiP involved in transport of proteins in nonmitochondrial compartments such as ER remained unaltered in response to mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of proteins involved in mitochondria-to-nucleus retrograde response in human cancer cells

Kulawiec

Arnouk²,

Desouki³

et al. 2006

cbt

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All tumors examined to date contain mutations in mitochondrial DNA (mtDNA). In addition, depletion of mtDNA is reported in a variety of tumors. Mitochondrial dysfunction resulting from changes in mtDNA invokes mitochondria-to-nucleus retrograde response in human cells. To identify proteins involved in retrograde response and their potential role in tumorigenesis, we carried out a comparative proteomic analysis using a cell line in which the mitochondrial genome was completely depleted (rho(0) cells lacking all mtDNA-encoded protein subunits), a cybrid cell line in which mtDNA was restored, and the parental cell line. Our comparative proteomic approach revealed marked changes in the cellular proteome and led us to identify quantitative changes in expression of several proteins. We found that subunits of complex I and complex III, molecular chaperones, and a protein involved in cell cycle control were downregulated and Inosine 5'-monophosphate dehydrogenase type 2 (IMPDH2) involved in nucleotide biosynthesis was upregulated in rho(0) cells. Our findings demonstrate that the expression of proteins is restored to wild type level by transfer of wild type mitochondria to rho(0) cells, suggesting that these proteins play key roles in retrograde response. To determine a potential role for identified retrograde responsive proteins in tumorigenesis, we analyzed the expression of UQCRC1 gene (encoding ubiquinol cytochrome-c reductase core protein I) in breast and ovarian tumors. We found that (1) UQCRC1 was highly expressed in breast (74%) and ovarian tumors (34%) and (2) the expression positively correlated with cytochrome c-oxidase (COXII) encoded by mtDNA. Our study opens an avenue for identification of retrograde proteins as potential tumor suppressors or oncogenes involved in carcinogenesis.

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“…It is not clear if the results retrieved from studies with small hydrophobic peptides can be generalized for the interaction of BiP with natural substrate proteins as well. A complex between an antibody domain and BiP showed that this substrate protein decelerates the hydrolysis step of the ATPase cycle (Mayer et al 2003).…”

Section: Modulation Of the Hsp70 Atpase Activitymentioning

confidence: 99%

Hsp70 and Hsp90—a relay team for protein folding

Wegele

Müller

Büchner

Reviews of Physiology, Biochemistry and Pharmacology

566

492

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Molecular chaperones are a functionally defined set of proteins which assist the structure formation of proteins in vivo. Without certain protective mechanisms, such as binding nascent polypeptide chains by molecular chaperones, cellular protein concentrations would lead to misfolding and aggregation. In the mammalian system, the molecular chaperones Hsp70 and Hsp90 are involved in the folding and maturation of key regulatory proteins, like steroid hormone receptors, transcription factors, and kinases, some of which are involved in cancer progression. Hsp70 and Hsp90 form a multichaperone complex, in which both are connected by a third protein called Hop. The connection of and the interplay between the two chaperone machineries is of crucial importance for cell viability. This review provides a detailed view of the Hsp70 and Hsp90 machineries, their cofactors and their mode of regulation. It summarizes the current knowledge in the field, including the ATP-dependent regulation of the Hsp70/Hsp90 multichaperone cycle and elucidates the complex interplay and their synergistic interaction.

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Modulation of the ATPase Cycle of BiP by Peptides and Proteins

Cited by 45 publications

References 50 publications

Conserved Structural and Functional Properties of D-domain Containing Redox-active and -inactive Protein Disulfide Isomerase-related Protein Chaperones

Conserved Structural and Functional Properties of D-domain Containing Redox-active and -inactive Protein Disulfide Isomerase-related Protein Chaperones

Proteomic analysis of proteins involved in mitochondria-to-nucleus retrograde response in human cancer cells

Hsp70 and Hsp90—a relay team for protein folding

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