- Open Access
Two classes of nucleic acid translocation motors: rotation and revolution without rotation
© Guo et al.; licensee BioMed Central Ltd. 2014
- Received: 11 September 2014
- Accepted: 11 September 2014
- Published: 16 September 2014
Biomotors are extensively involved in biological processes including cell mitosis, bacterial binary fission, DNA replication, DNA repair, homologous recombination, Holliday junction resolution, RNA transcription, and viral genome packaging. Traditionally, they were classified into two categories including linear and rotation motors. In 2013, a third class of motor by revolution mechanism without rotation was discovered. In this issue of “Structure and mechanisms of nanomotors in the cells”, four comprehensive reviews are published to address the latest advancements of the structure and motion mechanism of a variety of biomotors in archaea, animal viruses, bacteria, and bacteriophages.
- Bacteriophage phi29
- Hexameric ATPase
- DNA translocase
- DNA helicase
- Viral assembly
- DNA packaging
Nucleic acid translocation is ubiquitous in living systems. The motion required for these events is accomplished by biomotors hydrolyzing nucleotide (mainly ATP). Biomotors were once classified into two categories: linear and rotation motors. Accordingly, linear motors such as kinesin and myosin, seen in human and animal muscle coordination, move linearly, while rotation motors such as DNA helicases, F1/F0 ATPase, and bacterial flagella induce motion through a nut and bolt rotation mechanism. This concept of rotation for DNA translocation has been well-accepted in the field of biomotors due to the helical nature of the DNA with a 360° turn per pitch. The hypothesis that DNA packaging in dsDNA viruses was accomplished by such a five-fold/six-fold rotation motor survived for three decades. Numerous papers have been published in many high profile journals claiming the observation of five-fold viral motors with a rotation mechanism. However, attempts to evaluate this popular rotation mechanism has led to a wealth of contradictory experimental results. Gearing of the phi29 motor by a pRNA hexameric ring was revealed independently by both group of Peixuan Guo  and Dwight Anderson in 1998 , and highlighted in a minireview in Cell by the open-minded and visionary scientist Roger Hendrix , who even was the originator of the five-fold/six-fold rotation concept. In addition, biotechnological and single-molecule experiments revealed that neither the nut (motor channel/the viral connector) nor the bolt (dsDNA genome) rotate during packaging, thus, the rotation mechanism became an enigma.
As mentioned above, biomotors are ubiquitous in living systems and share many commonalities. In this special issue of Cell & Bioscience, the molecular mechanisms as well as biochemical and structural properties of a wide range of biomotors involved in archaeal DNA repair, dsDNA virus replication, viral and cellular SOS response, and double Holliday junction dissolution are comprehensively reviewed [20–23]. She et al. illustrate the structural analyses of archaeal nucleic acid biomotors in DNA damage repair and the molecular mechanisms of ATP hydrolysis promoting conformational change as the driving force of mechanical motion. Butcher et al. discuss a wide range of ATPases in the lifecycle of thermophilic archaeal dsDNA viruses from a bioinformatical, biochemical and structural point of view. This review in particular illustrates, how Sf2 helicases translocate along DNA in the classic fashion of rotation; while pointing out that in the phage phi29 packaging motor, the genome packaging ATPase of thermophilic viruses (e.g. B204), and FtsK cellular nanobiomotors, the revolution mechanism is applied. Weitao et al. review the structural and functional characteristics of viral and cellular SOS-regulated motor proteins with a focus on the relationship of translocation mechanism to motor function, while Costa et al. discuss the dissolvasome machinery in double Holliday junction dissolution and its molecular mechanism based on the structural interplay between its components. This review illustrates how the molecular mechanisms of Holliday junction related biomotors further differentiates rotation motors (RuvAB, BLM helicases) from revolution motors.
Revolution leads to a thermodynamic edge over rotation, especially in the translocation of lengthy dsDNAs and chromosomes. Due to the length of chromosomes, supercoiling of DNA by biomotors would be a major issue resulting in unnecessary energy consumption. Nature has elegantly evolved a revolution mechanism [4–8] devoid of rotation, torque, and coiling, thus minimizing work terms from molecular friction. The involvement of multiple enzymes in the Holliday junction resolution leads to a complicated motion mechanism. At present, it is controversial whether the Holliday junction dissolvasome motor uses the rotation or revolution mechanism, how many ATP molecules are used, and whether topoisomerases are involved in the DNA translocation process or only at the end of junction resolution . Tackling these questions is challenging due to the many motor components in the dissolvasome.
DNA translocation technology has tremendous potential in a range of biomedical applications, such as the diagnosis and treatment of cancers and viral diseases, as well as high-throughput human genome sequencing. Hopefully, the publication of this issue will be inspiring for the bio- and nanobiotechnology community and will facilitate the application of biomotors.
The authors would like to thank Dr. Gino Cingolani (Thomas Jefferson University), Dr. Pan Li (University at Albany, SUNY), Dr. Christopher I. Richards (University of Kentucky), Dr. Christopher M. Yengo (Pennsylvania State University), Dr. Chad Schwartz (Beckman Coulter), Dr. Alessandro Costa (London Research Institute), Dr. Qunxin She (University of Copenhagen) and Dr. Tao Weitao (Southwest Baptist University) for their constructive comments on the manuscript. The work was supported by NIH grant R01-EB003730, R01-EB012135, R01-EB019036, and U01-CA151648 to PG. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Funding to Peixuan Guo’s Endowed Chair in Nanobiotechnology position is from the William Fairish Endowment Fund.
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