6MI3
Structure of NEMO(51-112) with N- and C-terminal coiled-coil adaptors.
Summary for 6MI3
| Entry DOI | 10.2210/pdb6mi3/pdb |
| Descriptor | NF-kB ESSENTIAL MODULATOR,NF-kappa-B essential modulator,NF-kB ESSENTIAL MODULATOR (2 entities in total) |
| Functional Keywords | coiled coil, scaffolding, nf-kb pathway, transcription |
| Biological source | Homo sapiens More |
| Total number of polymer chains | 2 |
| Total formula weight | 29283.57 |
| Authors | Pellegrini, M.,Barczewski, A.H.,Mierke, D.F.,Ragusa, M.J. (deposition date: 2018-09-19, release date: 2019-07-31, Last modification date: 2023-10-11) |
| Primary citation | Barczewski, A.H.,Ragusa, M.J.,Mierke, D.F.,Pellegrini, M. The IKK-binding domain of NEMO is an irregular coiled coil with a dynamic binding interface. Sci Rep, 9:2950-2950, 2019 Cited by PubMed Abstract: NEMO is an essential component in the activation of the canonical NF-κB pathway and exerts its function by recruiting the IκB kinases (IKK) to the IKK complex. Inhibition of the NEMO/IKKs interaction is an attractive therapeutic paradigm for diseases related to NF-κB mis-regulation, but a difficult endeavor because of the extensive protein-protein interface. Here we report the high-resolution structure of the unbound IKKβ-binding domain of NEMO that will greatly facilitate the design of NEMO/IKK inhibitors. The structures of unbound NEMO show a closed conformation that partially occludes the three binding hot-spots and suggest a facile transition to an open state that can accommodate ligand binding. By fusing coiled-coil adaptors to the IKKβ-binding domain of NEMO, we succeeded in creating a protein with improved solution behavior, IKKβ-binding affinity and crystallization compatibility, which will enable the structural characterization of new NEMO/inhibitor complexes. PubMed: 30814588DOI: 10.1038/s41598-019-39588-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.783 Å) |
Structure validation
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