STRUCTURAL STUDIES OF DROSOPHILA ANAPLASTIC LYMPHOMA KINASE

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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.