Chaperones Proteins

Molecular Chaperones Proteins That Help Fold Glohular Proteins... 

FIGURE 6.36 A model for the steps involved in the folding of globular proteins. Chaperone proteins may assist in the initiation of the folding process. 

Wiech, H., Buchner, J., Zimmermann, R., Jakob, U. (1992). Hsp90 chaperones protein folding in vitro. Nature 358,169-170. 

The assembly of nucleosomes is mediated by one of several chromatin assembly factors facilitated by histone chaperones, proteins such as the anionic nuclear protein nucleoplasmin. As the nucleosome is assembled, histones are released from the histone chaperones. Nucleosomes appear to exhibit preference for certain regions on specific DNA molecules, but the basis for this nonrandom distribution, termed phasing, is not completely... 

The role of chaperone proteins in the folding of proteins is presented, and a model describing budding... 

A notable recently identified exception is copper (see Chapter 13) for which specific chaperone proteins deliver the metal to individual copper-dependant proteins (Harrison et al., 1999). 

In contrast to inhibitor 1, DARPP-32 and NIPP1, which regulate signal transduction, the function of inhibitor 2 appears to be different. There is evidence that inhibitor 2 associates with PP1, as the phosphatase is newly synthesized and contributes to the proper folding of the enzyme [40]. Inhibitor 2 can thus be considered a chaperone protein. The inactive PP 1-inhibitor 2 complex can then be activated upon phosphorylation of inhibitor 2 by glycogen synthase kinase-3. Whether this process is regulated in neurons in association with synaptic activity remains unknown. 

Figure 7.28 Wavefunction, Inc. Spartan 02 for Windows representation of the Atxl copper chaperone protein (PDB code 1FD8) with data from reference 116. See text for visualization details. Printed with permission of Wavefunction, Inc., Irvine, CA. (See color plate.)...

We will discuss in more detail in Chapter 8 how intracellular copper levels are maintained at extremely low levels by a series of copper chaperone proteins, which sequester newly assimilated copper within the cytoplasm of cells and deliver it in a targeted manner to be incorporated into specific copper-containing proteins. While copper uptake across the gastrointestinal tract is poorly understood—most probably utilising the divalent cation transporter... 

We have already described the plasma membrane systems employed in yeast for copper uptake, and here we briefly describe the chaperone proteins involved in the intracellular transport and delivery of copper to target proteins (Figure 8.10), which were first described... 

For Ras proteins, there is no chaperone protein available or known to solubilize the lipidated protein thus the refolding of, for example, lipidated N- and H-Ras is not feasible. However, lipidated K-Ras 110 can be generated via expressed protein ligation (EPL), since the polybasic C-terminal region of this protein helps to solubilize the protein even when farnesylated and facilitates the purification (Scheme 36). ... 

Proteins translated on the RER generally fold and assemble into subimits in the ER before being transferred to the Golgi apparatus. Other proteins fold in the cytoplasm. Molecular chaperones (proteins such as calnexin and BiP) assist in this process of protein folding. Proteins that are misfolded are targeted for destruction by ubiquitin and digested in cytoplasmic protein-digesting complexes called proteasomes. 

Heat-shock proteins (Hsps) are proteins expressed virtually in all organisms as a response of exposure to a stress, such as elevated temperature (fever), protein degradation, mechanical or chemical stress. As chaperone proteins they are concerned with the intracellular folding and refolding, assembly and translocation of damaged proteins. 

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