A single amino acid residue is responsible for species-specific incompatibility between CCT and alpha-actin.
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 (beta/gamma) actins but is now found to be incapable of folding mammalian skeletal muscle alpha-actin. Arrest of alpha-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 alpha-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.
Altschuler
G M
GM
Section of Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom.
Dekker
C
C
McCormack
E A
EA
Morris
E P
EP
Klug
D R
DR
Willison
K R
KR
D000199:Actins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001216:Asparagine / Q000378:metabolism; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013816:Thermodynamics
D000199:Actins; D000596:Amino Acids; D001216:Asparagine; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins