Altschuler G M, Dekker C, McCormack E A, Morris E P, Klug D R, Willison K R
Section of Cell and Molecular Biology, Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, United Kingdom.
FEBS Lett. 2009 Feb 18;583(4):782-6. doi: 10.1016/j.febslet.2009.01.031. Epub 2009 Feb 5.
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.
肌动蛋白依赖于II型伴侣蛋白CCT（含TCP-1的伴侣蛋白）来达到其天然状态。在体外，酵母CCT能折叠酵母肌动蛋白以及哺乳动物的细胞质（β/γ）肌动蛋白，但现在发现它无法折叠哺乳动物骨骼肌α-肌动蛋白。通过电子显微镜观察到α-肌动蛋白在酵母CCT上处于折叠周期中间体时会停滞。这一发现解释了之前在体内的观察结果，即仅表达肌肉肌动蛋白基因的酵母突变体无法存活。突变分析确定了一个单一的特定α-肌动蛋白残基Asn-297，它赋予了这种物种/异构体折叠特异性。本文讨论了这种不兼容性对伴侣蛋白机制和肌动蛋白-CCT共同进化的影响。
