Structure and mechanism of an exceptionally powerful molecular motor

多聚体ATPase驱动生物学机制，促进关键的生物合成途径，并控制细胞和病毒动力学。一种非常强大的多聚体ATPase是一种终止酶马达，在dsDNA病毒组装过程中将DNA泵入病毒衣壳。这些极其强大的终止酶为揭示马达输出的力量是如何支配的提供了独特的机会。对马达机制的了解可能会导致对环境做出反应的新纳米材料的开发，或者用于定向输送核酸的纳米设备的开发。此外，这些马达对利用纳米孔读出核酸序列的新测序技术的开发也很感兴趣。这个创新的研究和推广平台将探索末端酶的纳米技术潜力，同时也提供高中和研究生水平的教育机会。将结合X射线结晶学、低温电子显微镜和分子建模来阐明末端酶马达在原子水平上的结构机制，以确定末端及其复合体的三维结构。新的结构将被用来产生运动机制的假说，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+ATPase的研究，以揭示ATPase如何将化学能与机械运动相结合，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NSF的法定使命，并通过使用基金会的智力优势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.