Patel S S, Picha K M
Department of Biochemistry, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Annu Rev Biochem. 2000;69:651-97. doi: 10.1146/annurev.biochem.69.1.651.
Helicases are motor proteins that couple the hydrolysis of nucleoside triphosphate (NTPase) to nucleic acid unwinding. The hexameric helicases have a characteristic ring-shaped structure, and all, except the eukaryotic minichromosomal maintenance (MCM) helicase, are homohexamers. Most of the 12 known hexameric helicases play a role in DNA replication, recombination, and transcription. A human genetic disorder, Bloom's syndrome, is associated with a defect in one member of the class of hexameric helicases. Significant progress has been made in understanding the biochemical properties, structures, and interactions of these helicases with DNA and nucleotides. Cooperativity in nucleotide binding was observed in many, and sequential NTPase catalysis has been observed in two proteins, gp4 of bacteriophage T7 and rho of Escherichia coli. The crystal structures of the oligomeric T7 gp4 helicase and the hexamer of RepA helicase show structural features that substantiate the observed cooperativity, and both are consistent with nucleotide binding at the subunit interface. Models are presented that show how sequential NTP hydrolysis can lead to unidirectional and processive translocation. Possible unwinding mechanisms based on the DNA exclusion model are proposed here, termed the wedge, torsional, and helix-destabilizing models.
解旋酶是一类能将核苷三磷酸水解（NTP酶）与核酸解旋相偶联的驱动蛋白。六聚体解旋酶具有特征性的环状结构，除了真核生物的微小染色体维持（MCM）解旋酶外，其余均为同六聚体。已知的12种六聚体解旋酶中，大多数在DNA复制、重组和转录过程中发挥作用。一种人类遗传病——布卢姆综合征，与六聚体解旋酶家族中的一个成员缺陷有关。在理解这些解旋酶的生化特性、结构以及它们与DNA和核苷酸的相互作用方面已经取得了重大进展。在许多解旋酶中都观察到了核苷酸结合的协同性，并且在两种蛋白质中观察到了连续的NTP酶催化作用，即噬菌体T7的gp4蛋白和大肠杆菌的rho蛋白。寡聚T7 gp4解旋酶和RepA解旋酶六聚体的晶体结构显示出能够证实所观察到的协同性的结构特征，并且两者都与亚基界面处的核苷酸结合一致。文中提出了一些模型，展示了连续的NTP水解如何导致单向和持续性的移位。本文基于DNA排斥模型提出了可能 的解旋机制，即楔形模型、扭转模型和螺旋不稳定模型。
