Structure and mechanism of an exceptionally powerful molecular motor

多聚三磷酸腺苷酶驱动生物学机制，促进关键的生物合成途径和控制细胞和病毒动力学。在dsDNA病毒组装过程中，一种异常强大的多聚三磷酸腺苷酶是将DNA泵入病毒衣壳的末端酶马达。这些极其强大的终止酶为揭示运动输出的力量是如何被控制的提供了独特的机会。对运动机制的理解可能会导致对环境做出反应的新型纳米材料的开发，或者用于靶向递送核酸的纳米器件的开发。此外，这些马达对利用纳米孔读取核酸序列的新型测序技术的发展也很有兴趣。这个创新的研究和推广平台将探索终端的纳米技术潜力，同时也提供高中和研究生水平的教育机会。利用x射线晶体学、低温电子显微镜和分子模拟相结合的方法来确定端酶及其复合物的三维结构，在原子水平上阐明端酶马达的结构机制。新的结构将用于产生运动机制的假设，然后将使用创新的生化和生物物理分析进行测试。这些研究将补充研究人员对AAA+ atp酶的研究，揭示atp酶如何将化学能与机械运动结合起来，为分子马达的机制、调节和进化提供广泛而新颖的见解。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Multimeric ATPases drive the mechanics of biology, facilitating critical biosynthetic pathways and controlling cellular and viral dynamics. An exceptionally powerful multimeric ATPase is the terminase motor that pumps DNA into viral capsids during assembly of dsDNA viruses. These extremely powerful terminase enzymes provide unique opportunities for uncovering how the force of motor output is governed. Understanding of motor mechanism could lead to development of new nanomaterials that respond to the environment, or nanodevices for targeted delivery of nucleic acids. Furthermore, these motors are of interest in development of novel sequencing technologies using nanopores for reading out nucleic acid sequence. This innovative research and outreach platform will explore the terminase's nanotechnological potential, while also providing educational opportunities at the high school and graduate level.The structural mechanism of terminase motors at the atomic level will be elucidated using a combination of x-ray crystallography, cryo-electron microscopy and molecular modelling to determine three-dimensional structures of terminases and their complexes. New structures will be used to generate hypotheses for motor mechanism, which will then be tested using innovative biochemical and biophysical assays. These studies will complement the investigators research on AAA+ ATPases to reveal how ATPases couple chemical energy to mechanical motion, providing broad and novel insights into the mechanisms, regulation, and evolution of molecular motors.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.