On the origin of the Hsp70-lipid interaction: the yeast and bacterial connection
Mentor:Nikolas Nikolaidis, Associate Professor of Biological Science, California State University Fullerton
During periods of cellular stress proteins denature and eventually aggregate, which can ultimately lead to cell death. To combat these deleterious effects of stress, cells have evolved a complex stress response system consisting of several different families of proteins. One of the most evolutionarily conserved protein families in this system is the 70-kDa heat-shock proteins (Hsp70s). Hsp70s are molecular chaperones essential for cellular homeostasis and survival under both physiological and pathological conditions. Two well studied mammalian HSP70s, HSPA1A and HSPA8, have been found to also associate with cellular membranes, including the plasma, endosomal, and lysosomal membranes, where they bind to specific lipids. The association of HSPA1A with these lipids localizes and anchors the chaperone to the plasma membrane, stabilizes the lysosomal membrane, and plays a vital role in regulating immune responses and cell signaling. Furthermore, the binding of HSPA8 to endosomal membrane phospholipids is required for the chaperone-selective recruitment of proteins in late endosomes during microautophagy. Despite the essential role of extracellular or membrane-bound Hsp70s in immunogenic responses and cancer biology as well as cell signaling and survival, the biological importance of Hsp70-lipid interactions remains largely uncharacterized. Importantly, it remains unknown whether lipid-binding is a function evolutionarily conserved in yeast and bacterial Hsp70s. In this study we examined the lipid-binding properties of two yeast Hsp70s, the cytosolic SSA1 and the mitochondrial SSC1, and one bacterial Hsp70 (DnaK). Our data suggest that although SSA1 and DnaK bind to several anionic lipids, SSC1 does not. Although further experimentation is required to determine the affinities of these interactions, our results suggest that lipid-binding is an evolutionarily conserved property of Hsp70s and that Hsp70s are functionally differentiated with respect to their lipid-binding properties.