The Selective Inhibition of Serpin Aggregation by the Molecular Chaperone, α-Crystallin, Indicates a Nucleation-dependent Specificity

摘要: Abstract Small heat shock proteins (sHsps) are a ubiquitous family of molecular chaperones that prevent the misfolding and aggregation proteins. However, specific details about their substrate specificity mechanism chaperone action lacking. α1-Antichymotrypsin (ACT) α1-antitrypsin (α1-AT) two closely related members serpin superfamily aggregate through nucleation-dependent nucleation-independent pathways, respectively. The sHsp α-crystallin was unable to α1-AT, whereas inhibited ACT in dose-dependent manner. This selective inhibition coincided with formation stable high weight α-crystallin-ACT complex stoichiometry 1 on molar subunit basis. kinetics this interaction occur at same rate as loss monomer, suggesting monomeric species is bound by chaperone. 4,4′-Dianilino-1,1′-binaphthyl-5,5′-disulfonic acid (Bis-ANS) binding far-UV circular dichroism data suggest interacts specifically non-native conformation ACT. finding does not interact α1-AT under these conditions suggests displays for pathway, implying dynamic nature both its protein crucial factor other sHsps.