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Determination of the structure of IKK signaling complex by cryo-EM


EMSL Project ID
51534

Abstract

IKK complex serves as a central relay of signals from the membrane bound receptors, to regulate gene expression necessary for immune signaling and developmental processes. The ~270 kDa IKK complex contains kinases (IKK1 and/or IKK2) and a scaffold subunit NEMO. Structures of some domains of both kinases and NEMO are known; however, in absence of a structure of the IKK complex the mechanism of its activation during the signaling process is unclear. We seek to elucidate the activation mechanism of IKK complex through determination of its structure. In preliminary studies, we have produced rationally designed IKK complexes, prepared/screened limited grids, and obtained data that fetched only a low resolution cryo-EM map of IKK2 bound to a kinase binding domain of NEMO. We propose further screening to obtain suitable grids overcoming limitations of aggregation proneness and preferential orientation that predominantly underlie the low quality of our map

Project Details

Start Date
2020-06-15
End Date
2020-09-15
Status
Closed

Team

Principal Investigator

Gourisankar Ghosh
Institution
University of California, San Diego

Team Members

Tapan Biswas
Institution
University of California, San Diego