An unstructured C-terminal region of the hsp90 co-chaperone p23 is important for its chaperone function 1 1Edited by R. Huber

Weikl, Tina; Abelmann, Kerstin; Büchner, Johannes

doi:10.1006/jmbi.1999.3172

Cited by 96 publications

(110 citation statements)

References 24 publications

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“…2A). The CD spectra, which are similar to published spectra (31), are consistent with ␤-structure in the N-terminal domain together with an unstructured region at the C terminus (shown by the increase in the negative ellipticity at 202 nm for p23-(1-160). The positive ellipticity at ϳ230 nm is due to the high proportion of tryptophan residues (a total of 5) in the protein.…”

Section: Design and Characterization Of P23supporting

confidence: 84%

Localization of Sites of Interaction between p23 and Hsp90 in Solution

Martinez-Yamout

Venkitakrishnan

Preece

et al. 2006

Journal of Biological Chemistry

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Section: Design and Characterization Of P23supporting

confidence: 84%

Localization of Sites of Interaction between p23 and Hsp90 in Solution

Martinez-Yamout

Venkitakrishnan

Preece

et al. 2006

Journal of Biological Chemistry

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“…For Cpr6, suppression of aggregation was observed only at high ratios of Cpr6 to CS. This is reminiscent of p23, another protein that is found in complexes with Hsp90 (27,58). Both Cpr6 and Cpr7 slow down the thermal inactivation kinetics of CS, suggesting that they interact transiently with the substrate.…”

Section: Catalytic Activity Of the Large Immunophilins In The Accelermentioning

confidence: 98%

Cpr6 and Cpr7, Two Closely Related Hsp90-associated Immunophilins from Saccharomyces cerevisiae, Differ in Their Functional Properties

Mayr

Richter

Lilie

et al. 2000

Journal of Biological Chemistry

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106

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Hsp90 is an abundant cytosolic molecular chaperone. It controls the folding of target proteins including steroid hormone receptors and kinases in complex with several partner proteins. Prominent members of this protein family are large peptidyl prolyl cis/trans isomerases (PPIases), which catalyze the cis/trans isomerization of prolyl peptide bonds in proteins and possess chaperone activity. In Saccharomyces cerevisiae, two closely related large Hsp90-associated PPIases, Cpr6 and Cpr7, exist. We show here that these homologous proteins bind with comparable affinity to Hsp90 but exhibit significant structural and functional differences. Cpr6 is more stable than Cpr7 against thermal denaturation and displays an up to 100-fold higher PPIase activity. In contrast, the chaperone activity of Cpr6 is much lower than that of Cpr7. Based on these results we suggest that the two immunophilins perform overlapping but not identical tasks in the Hsp90 chaperone cycle. PPIases1 are enzymes that are able to catalyze the cis-trans isomerization of Xaa-Pro peptide bonds in short synthetic peptides as well as in proteins (1). The isomerization of these bonds is a slow process (2) and often a rate-determining step in protein folding (3-6). PPIases have been found in all organisms and subcellular compartments studied so far (1,7,8). Until now three unrelated families of PPIases could be identified: parvulins, cyclophilins, and FKBPs (1,5,9). Because of their inhibition by the immunosuppressive drugs cyclosporin A (CsA) or FK506/rapamycin, the cyclophilins and FKBPs are also termed immunophilins (10 -13). Several large immunophilins with a molecular mass of about 40 -54 kDa are components of the Hsp90 chaperone complex. In higher eukaryotes, FKBP51, FKBP52, and Cyp40 act together with Hsp90; in yeast these are Cpr6 and Cpr7, two cyclophilins. The Hsp90 complex seems to regulate the conformation of its target proteins. These substrates include steroid hormone receptors. Here, the Hsp90 chaperone cycle is well established (reviewed in Refs. 14 -16).In the case of the progesterone receptor, the receptor is bound to Hsp70 in an early complex (15,17). Then an intermediate complex is formed in which Hsp90, Hsp70, Hip, Hop, and perhaps Hsp40 participate. The last step of this activation cycle is a complex, consisting of the progesterone receptor, Hsp90, p23, and one of the large immunophilins. The specific function of the immunophilins in the chaperone cycle is far from clear. However, it is well established that progesterone receptor has to be bound in this complex to allow binding of the hormone, dimerization, and subsequently, interaction with DNA. In the absence of hormone, the receptor is released from the complex, and the cycle starts again. The large immunophilins interact with Hsp90 via tetratricopeptide repeats (18 -21). The partner site for the tetratricopeptide-repeat motifs is located in a 12-kDa carboxyl-terminal domain of Hsp90 (22, 23). The tetratricopeptide-repeat proteins compete with each other for this binding site (18,1...

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“…Work on human p23 indicated that the extreme carboxyl terminus is required for in vitro chaperone activity (13), whereas Sba1p's amino terminus mediates Hsp90 interactions (14). Thus, we purified two Sba1 carboxyl-terminal truncations (⌬50 or ⌬84).…”

Section: Sba1pmentioning

confidence: 99%

The p23 molecular chaperone promotes functional telomerase complexes through DNA dissociation

Toogun

Zeiger

Freeman

2007

Proc. Natl. Acad. Sci. U.S.A.

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Telomeres are the composite of short DNA element tandem arrays and heterotypic protein components that protect and maintain chromosomal termini. As proper telomere maintenance requires a multitude of DNA extension events, it is important to understand the factors that modulate telomerase DNA association. Here, we show that the endogenous levels of the yeast p23 molecular chaperone Sba1p are required for telomere length maintenance and that Sba1p can modulate telomerase DNA binding and extension activities in vitro. Notably, telomere occupancy by telomerase and the extension rate of a shortened telomere fluctuated with changing Sba1 protein levels in vivo. In addition, we found that Sba1p displayed a cell cycle-dependent telomere interaction that paralleled telomerase binding; telomere association by Sba1p depended on its inherent chaperone activity. Taken together, our results support a model in which Sba1p modulates telomerase DNA binding activity for optimal function in vitro and in vivo. DNA protein dynamicsT elomerase maintains genomic integrity, in part, by preserving chromosome length after DNA replication (1-3). Because conventional DNA polymerases require priming events to initiate synthesis, the extreme terminus of each lagging strand cannot be completed, which is commonly referred to as the end replication problem (4). In the absence of a compensatory process, this limitation would lead to chromosome erosion with each round of DNA replication. However, almost all eukaryotes circumvent this problem by adding simple DNA sequence motifs to each terminus that buffers against the loss. Typically the DNA motifs are added by the specialized ribonucleoprotein complex telomerase that is composed of a reverse transcriptase protein and an associated template RNA; in yeast, EST2 and TLC1 encode these factors. Depending on the organism, telomerase increases chromosome ends between a few hundred to a few thousand nucleotides to create, in part, a telomere. Perhaps unexpectedly, it was realized that the length of each telomere is not added at once but rather telomerase may append 6-8 nt per binding event (5). Although it had been argued that telomerase activity might not need to be iterative to maintain telomere length, recent studies in yeast indicate that telomeres can be extended over 100 nt per cell cycle (6, 7). Unfortunately, yeast telomerase does not add multiple repeats in vitro but rather extends a DNA substrate a single repeat and remains bound in a stalled state (5). Thus, the question is raised about how a bound telomerase complex is removed to allow the redundant binding and addition cycles necessary to support proper telomere maintenance.Prior studies indicated that the p23 and Hsp90 molecular chaperones are required for reconstitution of human telomerase activity in vitro (8, 9); unlike other telomerase cofactors the molecular chaperones seemingly remain associated during reverse transcription (9). A recent study indicates that the Hsp90 interaction might be necessary to promote telomerase DNA binding ...

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An unstructured C-terminal region of the hsp90 co-chaperone p23 is important for its chaperone function 1 1Edited by R. Huber

Cited by 96 publications

References 24 publications

Localization of Sites of Interaction between p23 and Hsp90 in Solution

Localization of Sites of Interaction between p23 and Hsp90 in Solution

Cpr6 and Cpr7, Two Closely Related Hsp90-associated Immunophilins from Saccharomyces cerevisiae, Differ in Their Functional Properties

The p23 molecular chaperone promotes functional telomerase complexes through DNA dissociation

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