Chaperone molecules

CS2], with increasing [CS2] kobs approached a maximum value. A rough estimate of K26 was made from the pressure of CS2 at which this value was attained. A similar recombination mechanism is envisaged for COS and NO, and estimated rate coefficients for the various chaperon molecules according to the above scheme are summarized in Table 5. In the case of COS it is not clear to what extent S(1 >) reactions contribute to the measured rate coefficients89. 

Typically, a series of steps is involved in the work carried out by chaperone molecules. Hsp70 operates on the protein as it is being formed on the ribosome. It recognizes extended or exposed protein chain regions that are more hydrophobic and acts to discourage unwanted association of these parts. It also acts to maintain the growing protein in a somewhat unfolded state. 

SERCA pumps sequester Ca2+ in the ER lumen By maintaining appropriate Ca2+ concentrations in the ER lumen, SERCA pumps also play an essential role in protein synthesis, folding and transport of membrane and secreted proteins. This involves in particular chaperone-dependent processing and post-translational modifications which require a unique calcium rich environment. Chaperone molecules such as calreticulin and calnexin are involved in the quality control pathway in the ER (Berridge, 2002 Ellgaard and Helenius, 2003 Michalak et al., 2002). 

An alternative hypothesis is that ER retention of Z-a,-anti trypsin results in autophagy, specifically of hepatic mitochondria. The basis for this hypothesis is the increase in autophagosomes in cells engineered for inducible expression of Z-tx,-antitrypsin. The mutant protein, along with the chaperone molecule calnexin, can be found in these autophagosomes by immune electron microscopy. It is postulated that mitochondrial dysfunction results from the damage to the mitochondria in the PIZZ liver, leading to the hepatic injury. 

COXl 7 copper carrying molecule for the mitochondria IMS intermembrane space of mitochondria, lying between the inner and outer membranes of this organelle Metal chaperone molecule that binds a specific metal and helps insert this ion into the metal binding site of a metalloprotein... 

Even neglecting the rather small contribution of reaction (xix) to the recombination in rich Ha—O2 systems, the breakdown of the constants k into their constituent third order rate coefficients is a matter of some difficulty. .Three chaperon molecules, Ha, HaO and the inert diluent, are involved in each of the reactions (xvii) and (xviii) and for some of these it is difficult in flames to vary sufficiently the burnt gas compositions in which the recombination occurs. Further, because of the equilibration of reaction (i), it is impossible to distinguish reaction (xvii) with M = HaO from (xviii) with M = Ha - The following discussion gives a likely overall picture based on results at present available, though detailed confirmation is necessary in some areas. 

Values of k near or below room temperature for a number of chaperon molecules M are given in Table 41. Added to the values from discharge—flow experiments are a number of results obtained recently from... 

In addition, the cellular localization of certain HDAC subtypes is governed by chaperone proteins (e.g., 14-3-3) which, depending on the phosphorylation state, transport the enzyme from the nucleus to the cytoplasm. Hence, inhibition of interaction with phosphatases, kinases, or chaperone molecules may also provide yet another avenue for regulation of HDAC activity with small-molecule ligands. 

FIGURE 3.8.3 As proteins are formed, chaperone molecules bind to them and assist them to fold in the proper way. These same chaperone molecules can recognize features of improperly folded proteins. Addition or removal of sugar molecules aids in the diagnosis. Incorrectly folded proteins may be either decomposed or fixed. (From Conn, P.M. and Janovick, J.A., Am. Sci., 93, 314, 2005. With permission.)... 

Understanding of chaperone molecules can help cure disease. 

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