Low sequence identity but high structural and functional conservation: The case of Hsp70/Hsp90 organizing protein (Hop/Sti1) of Leishmania braziliensis

Batista, Fernanda Aparecida Heleno; Seraphim, Thiago Vargas; Santos, Clelton A.; Gonzaga, Marisvanda R; Barbosa, Leandro R.S.; Ramos, Carlos Henrique Inácio; Borges, Júlio César

doi:10.1016/j.abb.2016.04.008

Cited by 9 publications

(6 citation statements)

References 57 publications

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“…The distance distribution function (Fig 3C ) indicates at least two stable domains with maxima at~3 and~5 nm within the D max of 240 Å. The D max obtained for PfHop falls within the range obtained for other Hop homologues; 180 Å for LbHop [42], 193 Å for Hop [43], 230 Å for PfHop [46] and 260 Å for STI1 [20]. Altogether, these values confirm Hop to generally assume an extended conformation across species.…”

Section: Low-resolution Structure Of Pfhop In Solutionsupporting

confidence: 73%

“…This was supported by predictions from BeStSel and Phyre2 (S1 Table ). The helical content estimated here for PfHop is comparable to that for Leishmania braziliensis Hop (LbHop) which was reported to be around 75% [42]. Notably, the PfHop helical content of 77% we observed here is much higher than that the 57% obtained for the same protein in a recent independent study [46].…”

Section: Analysis Of the Secondary Structure Of Pfhopsupporting

confidence: 72%

“…Notably, the PfHop helical content of 77% we observed here is much higher than that the 57% obtained for the same protein in a recent independent study [46]. While, it is not clear why such a wide discrepancy has been reported for PfHop helical content, our findings reconcile with that reported for its close homolog, LbHop [42]. Overall, the predominantly α-helical structure of PfHop is consistent with the predicted three-dimensional model of PfHop which showed that all its three TPR motifs are α-helical in nature [18].…”

Section: Analysis Of the Secondary Structure Of Pfhopcontrasting

confidence: 64%

“…Hop has been reported to exist as either monomer [21,41,42] or dimer [43,44], andas largely monomeric, forming weak dimers [45]. Based on size exclusion chromatography, PfHop eluted as an elongated monomer under reducing conditions.…”

Section: Oligomeric State Of Recombinant Pfhopmentioning

confidence: 99%

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Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers

et al. 2020

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Plasmodium falciparum causes the most lethal form of malaria. The cooperation of heat shock protein (Hsp) 70 and 90 is thought to facilitate folding of select group of cellular proteins that are crucial for cyto-protection and development of the parasites. Hsp70 and Hsp90 are brought into a functional complex that allows substrate exchange by stress inducible protein 1 (STI1), also known as Hsp70-Hsp90 organising protein (Hop). P. falciparum Hop (PfHop) co-localises and occurs in complex with the parasite cytosolic chaperones, PfHsp70-1 and PfHsp90. Here, we characterised the structure of recombinant PfHop using synchrotron radiation circular dichroism (SRCD) and small-angle X-ray scattering. Structurally, PfHop is a monomeric, elongated but folded protein, in agreement with its predicted TPR domain structure. Using SRCD, we established that PfHop is unstable at temperatures higher than 40˚C. This suggests that PfHop is less stable at elevated temperatures compared to its functional partner, PfHsp70-1, that is reportedly stable at temperatures as high as 80˚C. These findings contribute towards our understanding of the role of the Hop-mediated functional partnership between Hsp70 and Hsp90.

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Section: Low-resolution Structure Of Pfhop In Solutionsupporting

confidence: 73%

Section: Analysis Of the Secondary Structure Of Pfhopsupporting

confidence: 72%

Section: Analysis Of the Secondary Structure Of Pfhopcontrasting

confidence: 64%

Section: Oligomeric State Of Recombinant Pfhopmentioning

confidence: 99%

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Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers

et al. 2020

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“…Adicionalmente, na extremidade do DLPα há um segmento C-terminal intrinsecamente desordenado, de aproximadamente 30 resíduos de aminoácidos, que tem sido reportado por aumentar a sobrevivência celular e a atividade chaperona das Hsp70 (SMOCK; BLACKBURN; GIERASCH, 2011). Além disso, proteínas Hsp70 citossólicas e nucleares apresentam ao fim deste segmento um motivo EEVD envolvido na ligação destas à co-chaperonas que apresentam o motivo TPR (do inglês Tetratricopeptide repeat) (BATISTA et al, 2016).…”

Section: Composição Estrutural E Ciclo Funcional Das Hsp70unclassified

Caracterização estrutural, funcional e estabilidade térmica das proteínas humanas HspA5 e HspA8: uma abordagem comparativa

Silva¹

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Heat shock proteins (Hsps) are important components of cell protein quality control (PQC), acting on protein synthesis, folding, traffic and degradation. The central component in the PQC is the Hsp70 family, which consists of highly conserved, ubiquitous and ATP-dependent molecular chaperones. These chaperones can assume different conformations that are regulated by their dynamic association with the adenosine nucleotides (ATP and ADP), as well as by their interaction with cochaperones and client proteins. In humans there are several Hsp70 proteins, most of which are found in the cytoplasm, while others are specific for organelles. The objective of this work was to structurally and functionally characterize the cytosolic (HspA8) and endoplasmic reticulum (HspA5) human Hsp70 proteins, using similar methodologies.For this, the recombinant hHsp70 proteins were expressed, purified and then characterized for structure, stability and function by means of biophysical tests. The results show that the HspA5 and HspA8 proteins were produced in their folded form, with secondary structure content rich in α-helices and as slightly elongated monomers in solution. Such Hsp70 showed similar chemical and thermal stability, however two thermal transitions (Tm) were observed for HspA5 and three for HspA8, indicating structural differences that result in distinct thermal stability. Changes in secondary and tertiary structure were observed in the proteins under study in the presence of nucleotides, which also caused the thermal stabilization of hHsp70. The presence of Ca 2+ and Mg 2+ ions favored the binding of hHsp70 to ATP and ADP nucleotides in different ways, and unlike HspA5, the HspA8 protein interacted with Ca 2+ even in the absence of nucleotides. A process thermodynamically governed by enthalpy and entropy was observed for the interaction of the adenosine nucleotides with the HspA5 and HspA8 proteins. hHsp70 showed similar and relatively low ATP activity, however the affinity of HspA5 for ATP was higher than that of HspA8. Additionally, the HspA5 and HspA8 proteins were effective in preventing the aggregation of model client proteins, with different specificities. In summary, the data obtained demonstrate that, although they share 66% of identity, the human proteins HspA5 and HspA8 present structural and functional peculiarities, thus enriching the knowledge about such macromolecules.

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Hsp70/Hsp90 Organising Protein (Hop): Coordinating Much More than Chaperones

Schwarz

Baindur-Hudson

Blatch

et al. 2022

Subcellular Biochemistry

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Low sequence identity but high structural and functional conservation: The case of Hsp70/Hsp90 organizing protein (Hop/Sti1) of Leishmania braziliensis

Cited by 9 publications

References 57 publications

Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers

Biophysical analysis of Plasmodium falciparum Hsp70-Hsp90 organising protein (PfHop) reveals a monomer that is characterised by folded segments connected by flexible linkers

Caracterização estrutural, funcional e estabilidade térmica das proteínas humanas HspA5 e HspA8: uma abordagem comparativa

Hsp70/Hsp90 Organising Protein (Hop): Coordinating Much More than Chaperones

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