FIGURE 10.

Model highlighting role of Met¹⁴⁵ as a sensor in mediating recognition and degradation of CaM_ox by proteasome. The 20S proteasome complex composed of rings of α- (purple) and β- (blue) subunits in association with Hsp90 oligomers (tan) preferentially recognizes and degrades CaM_ox after oxidation of Met¹⁴⁵ to its sulfoxide (red dot). CaM_ox containing Met¹⁴⁵ in hydrophobic binding pocket (yellow) is targeted for degradation; intermediates indicative of the nonprocessive cleavage of CaM_ox include large fragments A¹-F⁸⁹ (not shown) and A¹-F⁹² as well as C-terminus peptides (G¹³²–K¹⁴⁸) enriched in Met(O)¹⁴⁵. Similar intermediates involving large CaM fragments are observed upon site-directed substitution of Met¹⁴⁴ and Met¹⁴⁵ with leucines (Fig. 6), consistent with a structural sensitivity at positions 144 or 145.