Chaperones binding capacity

The model in Figure 5 includes formation of both soluble and insoluble complexes of sHsp and substrate. The formation of insoluble sHsp/substrate complexes is consistent with the in vivo transition of sHsps to an insoluble, structure-bound form under many stress conditions as discussed above. At present we can provide only speculative explanations for this insolubility in the context of the chaperone model of sHsp function. From in vitro studies, it is clear that the ability of sHsps to keep substrates soluble is dependent on the sHsp-to-substrate ratio, the rate of substrate denaturation, and other factors in vitro conditions can be manipulated to cause precipitation of sHsp and substrate, as well as to maintain substrate solubility. Thus, insolubilization could result from a type of overload of the soluble binding capacity of the sHsps. Since in vivo there is good evidence that the insolubilization is reversible, this leads to the intriguing question of the mechanism of resolubilization, and whether this is also a function of Hsp70 systems, or if additional components are required. Alternatively, sHsp insolubilization in vivo could result from interaction with insoluble components in the cell. 

Chaperones. Figure 2 The multiple roles of BiP in the biogenesis of the secretory proteins. BiP, immunoglobulin heavy chain binding protein ER, endoplasmic reticulum ERAD, ER-associated degradation ERj, resident ER protein with J-domain Sec61, core subunit of the protein translocase UPR, unfolded protein response that involves several signal transduction pathways that are activated in order to increase the biosynthetic capacity and decrease the biosynthetic burden of the ER... 

The functions of the calcium-storage capacity of the ER are at least threefold the association of Ca2+ with Ca2+-binding proteins in the ER is part of a chaperone function that is essential for normal protein synthesis the rapid rate of Ca2+ uptake by endoplasmic pumps provides shortterm cytoplasmic Ca2+ buffering that resists untoward and transient changes in [Ca2+] and, finally, many signaling pathways employ elevated [Ca2+] to activate physiological processes. Extensive Ca2+ release from ER is coupled to activation of Ca2+ entry across the plasma membrane, a process known as capacitative calcium entry, which is discussed below. 

The sHsps are a diverse family of proteins, which are related by possession of a common, defined a-crystallin structural domain. While virtually all of these proteins share the capacity to act as chaperones by binding non-native proteins in an ATP-independent manner, evolutionary arguments and biochemical data indicate that they can interact with many different proteins to influence a potentially wide range of functions in different cells and organisms. In this regard, they are similar to other chaperones which, by the ability to bind diverse substrates, act to protect and/or to regulate multiple cellular processes. 

---