Structural basis for DNA duplex separation by a superfamily-2 helicase
Structural basis for DNA duplex separation by a superfamily-2 helicase
复制标题
DOI：
10.1038/nsmb1246
复制
发表时间：
2007-07-01
影响因子：
16.8
通讯作者：
Hopfner, Karl-Peter
中科院分区：
文献类型：
--
作者：
Buettner, Katharina;Nehring, Sebastian;Hopfner, Karl-Peter
为了揭示超家族2（SF 2）3 '->-> 5'解旋酶进行链分离的机制，我们测定了古细菌Hel 308的apo和DNAbound晶体结构，Hel 308是一种解旋滞后链的解旋酶，与人类DNA聚合酶θ有关。我们的结构捕获了双链体解旋反应，表明初始链分离不需要ATP，并将突出的β发夹环鉴定为解旋元件。丙型肝炎病毒NS 3解旋酶和RNA衰变因子中的类似环支持这种双链体解旋机制适用于SF 2解旋酶的广泛子集的想法。与ATP结合的SF 2酶的比较表明，ATP通过3'产物链的棘轮样转运促进1个碱基对的进行性解旋。我们的研究结果提供了第一个结构框架链分离的进行性SF 2的3 '-5'解旋酶，并揭示了重要的机械差异SF 1解旋酶。
To reveal the mechanism of processive strand separation by superfamily- 2 ( SF2) 3'->-> 5' helicases, we determined apo and DNAbound crystal structures of archaeal Hel308, a helicase that unwinds lagging strands and is related to human DNA polymerase theta. Our structure captures the duplex- unwinding reaction, shows that initial strand separation does not require ATP and identifies a prominent beta hairpin loop as the unwinding element. Similar loops in hepatitis C virus NS3 helicase and RNA- decay factors support the idea that this duplex- unwinding mechanism is applicable to a broad subset of SF2 helicases. Comparison with ATPbound SF2 enzymes suggests that ATP promotes processive unwinding of 1 base pair by ratchet- like transport of the 3' product strand. Our results provide a first structural framework for strand separation by processive SF2 3'- 5' helicases and reveal important mechanistic differences from SF1 helicases.