This refolding renders the PrP isoform extremely resistant to proteolysis. Holdases bind to protein folding intermediates to prevent their aggregation but without directly refolding them. The conserved domain may act as chaperones by unwinding RNA secondary structures and refolding properly. In case proper folding or refolding is impossible, HSPs mediate protein degradation. Chaperones help with protein refolding by providing a safe environment for the protein to fold. These protein bodies require refolding "in vitro" once extracted from "E.coli" cells by strong detergent. Tsavorite formed in a Neoproterozoic metamorphic event which involved extensive folding and refolding of rock.