The Mechanism of Intracellular Transport and Kinesin Motors, KIFs : Structure, Function, Dynamics and Regulation

一般来说，细胞内运输是细胞功能的基础。我们重点研究了激酶超家族蛋白（kinesin superfamily protein, KIFs）的作用机制。求解了13个新的kif的主要结构。利用分子细胞生物学和分子遗传学，我们发现KIF4是决定幼年神经元活性依赖性存活或死亡的关键分子，KIF26A作为GDNF/Ret信号的抑制因子对肠神经系统的发育至关重要，KIF17不仅通过运输NDMA受体发挥重要作用，而且通过运输NDMA受体，还通过CREB磷酸化和NR2A的泛素蛋白酶体依赖性降解来控制NR2B和KIF17的转录和翻译。我们解决了Mg^<++>ADP中的原子结构和Mg^<++>ADP中的水释放，因此我们解决了ATP水解过程中的几乎所有状态，这为我们理解kif如何沿着微管移动提供了强有力的基础。

Intracellular transport is fundamental for cellular functions in cells in general. We studied this mechanism focusing on the kinesin superfamily proteins (KIFs). The primary structures of 13 new KIFs were solved. Using molecular cell biology and molecular genetics we revealed that KIF4 is a key molecule determining activity dependent survival or death of juvenile neurons, that KIF26A is fundamental for development of enteric nervous system by acting as a suppressor for GDNF/Ret signaling, and that KIF17 plays a significant role by not only transporting NDMA receptors, but also controlling transcription and translation of NR2B and KIF17 through CREB phosphorylation and ubiquitin-proteasome dependent degradation of NR2A. We solved atomic structures during Mg^<++> and water release from Mg^<++>ADP so that we solved almost all states during ATP hydrolysis which gives us strong bases to understand how KIFs move along microtubules.