Sandbox chaperones: Difference between revisions
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Many chaperones are heat shock proteins (typically abbreviated as "Hsp" with the approximate molecular weight afterwards) that are expressed in response to high temperatures or other cellular stresses which impact protein folding. In these environments chaperones function to prevent or correct damage caused by misfolding and to prevent unwanted protein aggregation, which is more likely to happen when proteins are denatured by stress. Some heat shock protein chaperones are present at low to moderate levels in virtually all organisms at all times in order to help in essential protein maintenance. <ref>Ellis, R.J. and van der Vies, S.M. (1991). "Molecular chaperones". Annual Review of Biochemistry 60: 321–47</ref> | Many chaperones are heat shock proteins (typically abbreviated as "Hsp" with the approximate molecular weight afterwards) that are expressed in response to high temperatures or other cellular stresses which impact protein folding. In these environments chaperones function to prevent or correct damage caused by misfolding and to prevent unwanted protein aggregation, which is more likely to happen when proteins are denatured by stress. Some heat shock protein chaperones are present at low to moderate levels in virtually all organisms at all times in order to help in essential protein maintenance. <ref>Ellis, R.J. and van der Vies, S.M. (1991). "Molecular chaperones". Annual Review of Biochemistry 60: 321–47</ref> | ||
A special type of heat shock protein is | A special type of heat shock protein is Hsp90. Hsp90 is part of a chaperone complex with other general chaperones and functions to assist in the maturation of a select clientele of proteins. What exactly Hsp90 does to it's client proteins is the part of it's function that is still a mystery. Furthermore, a link between client proteins other than the fact that they all require Hsp90 to maintain active forms is of yet unknown.<ref>Goodsell, David. (2008). "Molecule of the Month: Hsp90." Education Portal of Protein Data Bank. doi: 10.2210/rcsb_pdb/mom_2008_12</ref> | ||
== Energetics == | == Energetics == | ||
[[Image:Hsp90.jpg|thumb|Conformational changes of Hsp90]] | |||
== Structural highlights == | == Structural highlights == | ||
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[[Image:1uym.png|thumb|1UYM with PU3 bound]] | [[Image:1uym.png|thumb|1UYM with PU3 bound]] | ||
Because many client proteins of the chaperone protein | Because many client proteins of the chaperone protein Hsp90 are involved in cellular growth, inhibition of the ATPase activity of Hsp90 is a potential strategy for the treatment of cancers. | ||
Geldanamycin is a natural product made by Streptomyces bacteria that blocks the binding of ATP to Hsp90, freezing the large conformational changes needed for function and causing complexes on Hsp90 and misfolded proteins to accumulate in the cytoplasm. These accumulated proteins are then targeted for degredation by the ubiquitin/proteosome system, which ultimately leads to cell death as a result of corrupted growth controlling signaling pathways. Unfortunately, geldanamycin is too toxic to normal body cells for use as an anticancer drug.<ref>Goodsell, David. (2008). "Molecule of the Month: Hsp90." Education Portal of Protein Data Bank. doi: 10.2210/rcsb_pdb/mom_2008_12</ref> | Geldanamycin is a natural product made by Streptomyces bacteria that blocks the binding of ATP to Hsp90, freezing the large conformational changes needed for function and causing complexes on Hsp90 and misfolded proteins to accumulate in the cytoplasm. These accumulated proteins are then targeted for degredation by the ubiquitin/proteosome system, which ultimately leads to cell death as a result of corrupted growth controlling signaling pathways. Unfortunately, geldanamycin is too toxic to normal body cells for use as an anticancer drug.<ref>Goodsell, David. (2008). "Molecule of the Month: Hsp90." Education Portal of Protein Data Bank. doi: 10.2210/rcsb_pdb/mom_2008_12</ref> | ||
