Heilman-Miller Susan L, Woodson Sarah A
Department of Chemistry and Biochemistry, University of Maryland, College Park, MD 20742-2021, USA.
J Mol Biol. 2003 Apr 25;328(2):385-94. doi: 10.1016/s0022-2836(03)00304-8.
The folding pathway of the Tetrahymena ribozyme correlates inversely with the sequence distance between native interactions, or contact order. The rapidly folding P4-P6 domain has a low contact order, while the slowly folding P3-P7 region has a high contact order. To examine the role of topology and contact order in RNA folding, we screened for circular permutants of the ribozyme that retain catalytic activity. Permutants beginning in the P4-P6 domain fold 5 to 20 times more slowly than the wild-type ribozyme. By contrast, 50% of a permuted RNA that disjoins a non-native interaction in P3 folds tenfold faster than the wild-type ribozyme. Hence, the probability of rapidly folding to the native state depends on the topology of tertiary domains.
嗜热四膜虫核酶的折叠途径与天然相互作用之间的序列距离或接触顺序呈负相关。快速折叠的P4 - P6结构域具有较低的接触顺序,而缓慢折叠的P3 - P7区域具有较高的接触顺序。为了研究拓扑结构和接触顺序在RNA折叠中的作用,我们筛选了保留催化活性的核酶环形置换突变体。起始于P4 - P6结构域的置换突变体折叠速度比野生型核酶慢5至20倍。相比之下,一种置换RNA断开了P3中的非天然相互作用,其50%的折叠速度比野生型核酶快10倍。因此,快速折叠成天然状态的概率取决于三级结构域的拓扑结构。