A single amino acid residue is responsible for species-specific incompatibility between CCT and α-actin

Abstract 

Actin is dependent on the type-II chaperonin CCT (chaperonin containing TCP-1) to reach its native state. In vitro, yeast CCT folds yeast and also mammalian cytoplasmic (β/γ) actins but is now found to be incapable of folding mammalian skeletal muscle α-actin. Arrest of α-actin on yeast CCT at a folding cycle intermediate has been observed by electron microscopy. This discovery explains previous observations in vivo that yeast mutants expressing only the muscle actin gene are non-viable. Mutational analysis identified a single specific α-actin residue, Asn-297, that confers this species/isoform folding specificity. The implications of this incompatibility for chaperonin mechanism and actin–CCT co-evolution are discussed.

Keywords: Actin, ACT1, Muscle, CCT, Chaperonin, Protein folding