Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3. Export

@article{citeulike:1284109, 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.}, address = {Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, author = {Bouyain, S. and Leahy, D. J.}, citeulike-article-id = {1284109}, citeulike-linkout-0 = {http://dx.doi.org/10.1110/ps.062700307}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17384230}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17384230}, doi = {10.1110/ps.062700307}, issn = {0961-8368}, journal = {Protein Sci}, keywords = {40061086, edificios, estructuras, innovacion, vigas}, month = {April}, number = {4}, pages = {654--661}, posted-at = {2007-05-11 21:48:58}, priority = {1}, title = {Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3.}, url = {http://dx.doi.org/10.1110/ps.062700307}, volume = {16}, year = {2007} }

TY - JOUR ID - citeulike:1284109 L3 - citeulike-article-id:1284109 N2 - 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. IS - 4 JF - Protein Sci SN - 0961-8368 AD - Department of Biophysics and Biophysical Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. EP - 661 TI - Structure-based mutagenesis of the substrate-recognition domain of Nrdp1/FLRF identifies the binding site for the receptor tyrosine kinase ErbB3. VL - 16 SP - 654 KW - 40061086 KW - edificios KW - estructuras KW - innovacion KW - vigas AU - Bouyain, S AU - Leahy, DJ PY - 2007/04// UR - http://dx.doi.org/10.1110/ps.062700307 ER -