2OGB

Crystal structure of the C-terminal domain of mouse Nrdp1

Summary for 2OGB

• Entry DOI: 10.2210/pdb2ogb/pdb
• Descriptor: RING finger protein 41, THIOCYANATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: e3 ubiquitin ligase, receptor-binding region, ligase
• Biological source: Mus musculus (house mouse)
• Total number of polymer chains: 2
• Total formula weight: 29257.41

Authors

Bouyain, S.,Leahy, D.J. (deposition date: 2007-01-05, release date: 2007-01-16, Last modification date: 2024-11-06)

Primary citation

Bouyain, S.,Leahy, D.J.
Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3.
Protein Sci., 16:654-661, 2007

PubMed Abstract: The E3 ubiquitin ligase neuregulin receptor degrading protein 1 (Nrdp1) mediates the ligand-independent degradation of the epidermal growth factor receptor family member ErbB3/HER3. By regulating cellular levels of ErbB3, Nrdp1 influences ErbB3-mediated signaling, which is essential for normal vertebrate development. Nrdp1 belongs to the tripartite or RBCC (RING, B-box, coiled-coil) family of ubiquitin ligases in which the RING domain is responsible for ubiquitin ligation and a variable C-terminal region mediates substrate recognition. We report here the 1.95 A crystal structure of the C-terminal domain of Nrdp1 and show that this domain is sufficient to mediate ErbB3 binding. Furthermore, we have used site-directed mutagenesis to map regions of the Nrdp1 surface that are important for interacting with ErbB3 and mediating its degradation in transfected cells. The ErbB3-binding site localizes to a region of Nrdp1 that is conserved from invertebrates to vertebrates, in contrast to ErbB3, which is only found in vertebrates. This observation suggests that Nrdp1 uses a common binding site to recognize its targets in different species.

PubMed: 17384230
DOI: 10.1110/ps.062700307

Experimental method

X-RAY DIFFRACTION (1.95 Å)