Synechocystis HSP17 is an amphitropic protein that stabilizes heat-stressed membranes and binds denatured proteins for subsequent chaperone-mediated refolding

The small heat shock proteins (sHSPs) are ubiquitous stress proteins propos ed to act as molecular chaperones to prevent irreversible protein denaturat ion. We characterized the chaperone activity of Synechocystis HSP17 and fou nd that it has not only protein-protective activity, but also a previously unrecognized ability to stabilize lipid membranes. Like other sHSPs, recomb inant Synechocystis HSP17 formed stable complexes with denatured malate deh ydrogenase and served as a reservoir for the unfolded substrate, transferri ng it to the DnaK/DnaJ/GrpE and GroEL/ES chaperone network for subsequent r efolding. Large unilamellar vesicles made of synthetic and cyanobacterial l ipids were found to modulate this refolding process. Investigation of HSP17 -lipid interactions revealed a preference for the liquid crystalline phase and resulted in an elevated physical order in model lipid membranes. Direct evidence for the participation of HSP17 in the control of thylakoid membra ne physical state in vivo was gained by examining an hsp17(-) deletion muta nt compared with the isogenic wild-type hsp17(+) revertant Synechocystis ce lls. We suggest that, together with GroEL, HSP17 behaves as an amphitropic protein and plays a dual role. Depending on its membrane or cytosolic locat ion, it may function as a "membrane stabilizing factor" as well as a member of a multichaperone protein-folding network. Membrane association of sHSPs could antagonize the heat-induced hyperfluidization of specific membrane d omains and thereby serve to preserve structural and functional integrity of biomembranes.