Fig. 1.

SOD1 forms nonnative trimer. (A) HS-AFM analysis reveals that under stabilizing conditions (pH 3.5), SOD1 oligomer features a tripartite structure, in line with volumetric AFM measurements of dry samples, where oligomer volume is ∼71.7 nm³ and monomer volume is ∼25.3 nm³ (Fig. S1A). We observe three distinct monomers in HS-AFM recordings at a SOD1 concentration of 30 nM. The three subunits form a nonspherical compact particle, which is stable over long time periods. (Scale bar: 5 nm.) (B) In destabilizing conditions (pH 7.4), SOD1 trimers dissociate into three distinct monomers, even at the high end of physiological concentration (100 nM). (Scale bar: 5 nm.)