Abstract

Ring-shaped hexameric helicases are essential motor proteins that separate duplex nucleic acid strands for DNA replication, recombination, and transcriptional regulation. Two evolutionarily distinct lineages of these enzymes, predicated on RecA and AAA+ ATPase folds, have been identified and characterized to date. Hexameric helicases couple NTP hydrolysis with conformational changes that move nucleic acid substrates through a central pore in the enzyme. How hexameric helicases productively engage client DNA or RNA segments and use successive rounds of NTPase activity to power translocation and unwinding have been longstanding questions in the field. Recent structural and biophysical findings are beginning to reveal commonalities in NTP hydrolysis and substrate translocation by diverse hexameric helicase families. Here, we review these molecular mechanisms and highlight aspects of their function that are yet to be understood.

摘要

环状六聚体解旋酶是必需的马达蛋白，可分离双链核酸链以进行 DNA 复制、重组和转录调控。这些酶的两个进化上不同的谱系，以 RecA 和 AAA+ ATP 酶折叠为基础，迄今已被鉴定和表征。六聚体解旋酶将 NTP 水解与构象变化相结合，使核酸底物通过酶的中心孔。六聚体解旋酶如何有效地接合客户 DNA 或 RNA 片段并使用连续几轮 NTPase 活性来驱动易位和解旋一直是该领域长期存在的问题。最近的结构和生物物理学发现开始揭示不同六聚体解旋酶家族在 NTP 水解和底物易位中的共性。这里，