Information AboutHsp70 |
| CATEGORIES ABOUT HSP70 | |
| heat shock proteins | |
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DISCOVERY Members of the Hsp70 family are strongly upregulated by heat stress and Toxic chemicals, particularly heavy metals such as arsenic, cadmium, copper, mercury, etc. Hsp70 was originally discovered by FM Rotissa in the 1960s when a lab worker accidentally boosted the incubation temperature of Drosophila (fruit flies). When examining the chromosomes, Rotissa found a "puffing pattern" indicated heightened gene transcription. This was later described at the Heat Shock Response (i.e. Hsp proteins). STRUCTURE All of the Hsp70 proteins have three major functional domains.
FUNCTION AND REGULATION When not interacting with a substrate peptide, Hsp70 is usually in an ATP bound state. Hsp70 by itself is characterized by a very weak ATPase activity, such that spontaneous hydrolysis will not occur for many minutes. As newly synthesized proteins emerge from the Ribosome s, the substrate binding domain of Hsp70 recognizes sequences of hydrophobic amino acid residues, and interacts with them. This spontaneous interaction is reversible, and in the ATP bound state Hsp70 may relatively freely bind and release peptides. However, the presence of a peptide in the binding domain stimulates the ATPase activity of Hsp70, increasing its normally-slow rate of ATP hydrolysis. When ATP is hydrolyzed to ADP the binding pocket of Hsp70 closes, tightly binding the now-trapped peptide chain. Further speeding ATP hydrolysis are the so-called J-domain cochaperones: primarily Hsp40 in eukaryotes, and DnaJ in prokaryotes. These cochaperones dramatically increase the ATPase activity of Hsp70 in the presence of interacting peptides. By binding tightly to partially-synthesized peptide sequences (incomplete proteins), Hsp70 prevents them from aggregating and being rendered nonfunctional. Once the entire protein is synthesized, a Nucleotide Exchange Factor (BAG-1 and HspBP1 are among those which have been identified) stimulates the release of ADP and binding of fresh ATP, opening the binding pocket. The protein is then free to fold on its own, or to be transferred to other chaperones for further processing. HOP (the ''Hsp70/Hsp90 O'''rganizing '''P'''rotein) can bind to both Hsp70 and Hsp90 at the same time, and mediates the transfer of peptides from Hsp70 to Hsp90. Hsp70 also aids in transmembrane transport of proteins, by stabilizing them in a partially-folded state. Hsp70 proteins can act to protect cells from thermal or oxidative stress. These stresses normally act to damage proteins, causing partial unfolding and possible aggregation. By temporarily binding to hydrophobic resides exposed by stress, Hsp70 prevents these partially-denatured proteins from aggregating, and allows them to refold. Finally, Hsp70 seems to be able to participate in disposal of damaged or defective proteins. Interaction with CHIP (''C''arboxyl-terminus of ''H''sp70 ''I''nteracting ''P''rotein)–an E3 Ubiquitin Ligase –allows Hsp70 to pass proteins to the cell's Ubiquitin ation and Proteolysis pathways. FAMILY MEMBERS Eukaryotic organisms express several slightly different Hsp70 proteins. All share the common domain structure, but each has a unique pattern of expression or subcellular localization.
Prokaryotes express a single Hsp70 protein, DnaK. SEE ALSO EXTERNAL LINKS
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