Heat shock protein domains

Li, G.C., Li, L.G., Liu, R.Y., Rehman, M., Lee, W.M. (1992). Heat shock protein hsp70 protects cells from thermal stress even after deletion of its ATP binding domain. Proc. Natl. Acad. Sci. USA 89,2036-2040. 

Both the heat and cold shock response are universal and have been studied extensively. The major heat shock proteins (HSPs) are highly conserved. They are involved in the homeostatic adaptation of cells to harsh environmental conditions. Some act as molecular chaperones for protein folding, while others are involved in the processing of denatured polypeptides whose accumulation would be deleterious. The cold shock results in the transient induction of cold shock proteins (CSPs), which include a family of small acidic proteins carrying the cold shock domain. The CSPs appear to be involved in various cellular functions such as transcription, translation and DNA recombination. 

VASP, vasodilator stimulated phosphoprotein hsp27, heat shock protein hsp27 LASP, LIM and SH3 domain containing protein Tx, thromboxane IP3, inositol triphosphate ADP, adenosine 5 -diphosphate. Adapted from Refs. [44] and [116]. 

Bork, P., Sander, C., and Valencia, A. (1992). An ATPase domain common to prokaryotic cell cycle proteins, sugar kinases, actin, and hsp70 heat shock proteins. Proc. Natl. Acad. Sci. U.S.A. 89, 7290-7294. 

Photocrosslinkers have been incorporated in E. coli to confirm close contact between specific residues of a protein and its substrate. ClpB, a heat shock protein that aids in the disaggregation and refolding of proteins during the heat shock response, has a conserved aromatic residue (Tyr251) in the central pore of its AAA+ domain, considered to be the main substrate recognition residue. " After Tyr251 in ClpB was replaced with />BpA, biotinylated substrate peptides were shown to be crosslinked upon UV light exposure, but not if BpA was incorporated elsewhere in the AAA+ domain of this protein. 

Grenert JP, Sullivan WP, Fadden P, et al. (1997) The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem. 272, 23843-23850. 

Upon entering the cell, the steroid molecule initially binds to the steroid receptor protein (E domain) to form the steroid-hormone-receptor complex. This complex concomitantly binds to an additional eight or more other peptides (also via the E domain) these peptides are termed chaperone peptides and consist of macromolecules such as heat shock proteins (e.g., hsp70, hsp90). The chaperone peptides help to twist and turn the steroid receptor protein into an improved three-dimensional shape for final and optimal binding of the steroid molecule. Following binding of the chaperone peptides, the steroid-hormone-receptor complex becomes a mature steroid-hormone-receptor... 

Activation of steroid hormone receptors by the hormone. In the absence of the hormone, the steroid receptors are complexed through the hormone-binding domain to another protein known as heat shock protein 90 (hsp90). Both the hormone-binding domain and the hsp90 prevent functional interaction of the receptor with DNA. Binding of the hormone frees the receptor from hsp90 and promotes dimerization of the receptor, which can then bind to the palindromic hormone response element (HRE) and activate transcription. 

Marcu, M.G. et al. 2000. The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone. J. Biol. Chem. 275, 37181-37186. 

In summary, the KinaTor technology appears to be extremely potent for potentially revealing all binding partners of biologically active kinase inhibitors. Transmembrane domain proteins bind, as well as lipid kinases and other nucleotidebinding proteins, such as heat-shock proteins and oxidoreductases (unpublished data). So far, there are no limitations. 

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