多个 RPA 使 WRN 综合征蛋白成为超螺旋酶。

Center for Nano-Bio Measurement, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.

Department of Physics and Astronomy, Institute of Applied Physics, National Center of Creative Research Initiatives, Seoul National University, Seoul, Republic of Korea.

Nucleic Acids Res. 2018 May 18;46(9):4689-4698. doi: 10.1093/nar/gky272.

RPA is known to stimulate the helicase activity of Werner syndrome protein (WRN), but the exact stimulation mechanism is not understood. We use single-molecule FRET and magnetic tweezers to investigate the helicase activity of WRN and its stimulation by RPA. We show that WRN alone is a weak helicase which repetitively unwind just a few tens of base pairs, but that binding of multiple RPAs to the enzyme converts WRN into a superhelicase that unidirectionally unwinds double-stranded DNA more than 1 kb. Our study provides a good case in which the activity and biological functions of the enzyme may be fundamentally altered by the binding of cofactors.

RPA 已知能刺激 Werner 综合征蛋白 (WRN) 的解旋酶活性，但具体的刺激机制尚不清楚。我们使用单分子 FRET 和磁镊研究了 WRN 的解旋酶活性及其被 RPA 的刺激作用。结果表明，WRN 本身是一种弱解旋酶，只能反复解开几十个碱基对，但多个 RPA 与该酶结合后，将 WRN 转化为单链 DNA 解旋酶，可单向解开超过 1 kb 的双链 DNA。本研究为一个很好的案例，其中酶的活性和生物学功能可能会因辅助因子的结合而从根本上改变。