Potential sHsp Substrates

A considerable gap remains between in vitro studies of sHsp chaperone function and our understanding of how sHsps function in vivo. An important outstanding question is With what substrates do sHsps interact in vivo The variations in sHsp structure and expression are consistent 

The conserved Arg residue linked to cataract and myopathy can now be considered in the context of the two determined sHsp structures. However, the structural contacts made by this residue differ significantly 

cerevisiae deletion of. VI Isp26 alone or in combination with 5cHsp42 leads to no measurable defect in tolerance to a variety of stresses (Petko and Lindquist, 1985 Susek and Lindquist, 1989 Wotton et al., 1996 E. Vierling, unpublished observations). Deletion of 5cHsp26 also 

In addition to their potential to interact with non-native proteins in a chaperone capacity, a recent hypothesis postulates that sHsps interact with membranes to reduce high-temperature—induced membrane fluidity (Torok et al., 2001 Vigh et al., 1998). Membranes are clearly an important cellular component perturbed by heat, and a need for membrane stabilization is logical. Changes in membrane composition and correlated fluidity in S. cerevisiae and Synechocystis change the set point  

Direct interaction of sHsps other than a-crystallin with membranes has been reported only for Synechocystis Hsp 16.6 (Torok et al., 2001). Purified recombinant protein interacted with lipid vesicles, as monitored by fluorescence anisotropy, to reduce lipid fluidity and also increased the surface pressure of lipid monolayers. There was evidence for both lipid specificity and membrane penetration of the sHsp. Thylakoids isolated from cells deleted for Hsp 16.6 were more fluid membranes than wild-type cells, even in the presence of very little sHsp. Ability to stabilize directly photosynthetic membranes by lipid interaction could explain data supporting a role for sHsps in photosystem II protection, but the specificity of this effect has not been very well documented (Harndahl and Sundby, 2001 Heckathorn et al., 1998 Lee et al., 2000 Nakamoto et al., 2000). 

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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. 

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