What is it about?

In this work we determine the structure of the domain of NEMO responsible for binding the partner kinases IKK alpha and beta by X-ray crystallography. This is the first structure of NEMO in the unbound form and it was achieved thanks to the design of an engineered construct which utilizes ideal coiled-coil adapters to stabilize the NEMO domain. The NEMO helical dimer "clamps-up" in a more closed conformation in the unbound form, occluding the IKK-beta binding hot-spots. Nonetheless irregularities in the coiled-coil structure and enhanced dynamics reveal adaptability of teh structure to adopt a more open conformation to bind the ligands.

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Why is it important?

The new constructs developed not only help elucidate the structure of the unbound NEMO, but open the way to the crystallization of NEMO in complex with small molecule inhibitors to be used for rational inhibitor design and optimization.

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This page is a summary of: The IKK-binding domain of NEMO is an irregular coiled coil with a dynamic binding interface, Scientific Reports, February 2019, Springer Science + Business Media, DOI: 10.1038/s41598-019-39588-2.
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