STRUCTURAL STUDIES OF DROSOPHILA ANAPLASTIC LYMPHOMA KINASE

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 间变性淋巴瘤激酶(ALK)在多种细胞功能中起着关键作用，与人类癌症的发生密切相关。本项目旨在了解果蝇ALK(DALK)与其已知的配体果冻腹(JEIB)结合和激活的分子机制。到目前为止，人们对道尔克的结构一无所知。在这个拟议的实验中，我想使用SAXS来识别DALK的全局形状。DALK中的各个区域都有几种晶体结构。因此，通过确定DALK的整体形状，就有可能将单个结构域的晶体结构匹配到整个SAXS模型中。这些数据将提供DALK的第一个结构视图，并将阐明Jeb如何与DALK结合并激活DALK的分子机制。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Anaplastic lymphoma kinase(ALK) plays key roles in various cellular functions and is implicated in human cancers. This project aims to understand the molecular mechanism of binding and activation of Drosophila ALK (dALK) by its known ligand jelly belly (jeb). Nothing is known about the struture of dALK so far. In this proposed experiment, I would like to use SAXS to identify the global shape of dALK. Several crystal structures are available for individual domains in dALK. So by identifying the global shape of dALK, it's possible to then fit the crystal structure of individual domain into the overall SAXS model. These data will provide the first structural view of dALK and will shed light on the molecular mechanism of how jeb binds to and activates dALK.