Structural characterization of pseudokinase-containing receptors.

Pseudokinases are inactive kinases that play crucial roles in human biology and various human diseases, such as cancers. However, our lack of understanding of their mechanisms of action limits our current ability to target them in the clinic. I aim to decipher the molecular mechanisms of pseudokinase-containing receptors by cryo-electron microscopy. Their structures will inform us how these receptors function and how their dysregulation leads to human diseases. Additionally, these studies will teach us how to target their pseudokinase domain to modulate the activity of the receptors, which may lead to new therapeutic avenues.

假激酶（pseudokinase）是一类丧失催化活性的激酶，在人类生物学进程及癌症等多种人类疾病中发挥关键调控作用。然而，当前学界对其作用机制的认知缺口，限制了临床靶向干预这类靶点的实际能力。本研究拟通过冷冻电镜（cryo-electron microscopy）技术，解析含假激酶结构域的受体的分子机制。此类受体的三维结构将揭示其生理功能的运作逻辑，以及其失调状态如何诱发人类疾病。此外，本研究还将阐明靶向其假激酶结构域以调控受体活性的可行策略，这有望为开发新型治疗手段开辟全新路径。