This webpage was produced as an assignment for an undergraduate course at Davidson College
Hsp90 Orthologs
Hsp90 is a very highly conserved protein in species that it has been studied in. Although there is some amino acid diversity among different orthologs of Hsp90, these changed amino acids usually do not interfere with the function of the protein. In some cases, such as the comparison of human Hsp90 and mouse (Mus musculus) Hsp90, there is no difference at all. A protein BLAST of the sequence of human Hsp90 shows that human and mouse Hsp90 are 100% identical to one another. Because both organisms are mammals and have a relatively recent common ancestor, this result is somewhat expected, but it still speaks to the conservative nature of Hsp90. Along these expected lines, it seems that all vertebrates have about at least 95% identity of the protein between them, and the amino acid differences are in the variable length charged linker region that does not have a significant impact on the protein’s function (Garnier et al 2002).
Human Hsp90 has also been compared significantly with the well-studied fungus yeast (Saccharomyces cerevisiae). The amino acid identity of yeast Hsp90 when compared to human Hsp90 is only about 60%, much less than that of a mouse or other vertebrate. However, the three-dimensional stuctures of human and yeast Hsp90 are almost identical to one another. This suggests that the mutations in the amino acid sequence do not affect the overall function of the protein, further demonstrating the conservative nature of Hsp90 (Garnier et al 2002).
Hsp90 has also been seen and isolated in various plant species. In general, comparisons of plant amino acid sequences have shown a range of 88-93% identity when compared to each other, as well as a 63-71% amino acid identity when compared to sequences of yeast and human Hsp90. Among the highly studied plants is Arapidopsis thaliana, which lies within those ranges in terms of amino acid identity. Further analysis of Arapidopsis thaliana shows the conservation of the binding sites at the N-terminus and C-terminus as well as the charged linker region. Although the specific activity of plant Hsp90 has not been thoroughly studied, the conservation of these important regions of the protein suggest a similar function (the ability to bind p23 has been shown in plant Hsp90, for example) (Krishna and Gloor 2001).
Although prokaryotes such as E. coli do not have the specific Hsp90 protein, they do have HtpG, an ortholog of Hsp90 found in prokaryotes. HtpG has about 42% identity in amino acid sequence to human Hsp90. However, unlike the various forms of Hsp90, prokaryotic HtpG has a significant change at the C-terminal region of the protein. HtpG is missing the amino acid sequence MEEVD, a sequence that is believed to be important for the localization of the protein. Hsp90 is primarily found in the cytoplasm, while prokaryotic HtpG can be dispensed outside of the cell (Krishna and Gloor 2001).
One more ortholog of Hsp90 that is found in a wide variety of organisms is the glucose regulating protein Grp94. Grp94 shows a 50% amino acid identity with human Hsp90, but has a significantly different function as well as being localized in the endoplasmic reticulum as opposed to the cytoplasm (Krishna and Gloor 2001).
References
Garnier, Cyrille, Lafitte, Daniel, Tsvetkov, Philipp O., Barbier, Pascale, Leclerc-Devin, Jocelyne, Millot, Jean-Mare, Briand, Claudette, Makarov, Alexander A., Catelli, Maria G., and Vincent Peyrot. 2002. Binding of ATP to Heat Shock Protein 90: Evidence fo an ATP-Binding Site in the C-Terminal Domain. The Journal of Biological Chemistry. Vol. 277, no. 14, pp. 12208-12214.
Krishna, Priti and Greg Gloor. 2001. The Hsp90 family of proteins in Arapidopsis thaliana. Cell stress and Chaperones. Vol 6, pp. 238-246.