4xxb
From Proteopedia
Crystal structure of human MDM2-RPL11
Structural highlights
DiseaseRL11_HUMAN Blackfan-Diamond disease. Diamond-Blackfan anemia 7 (DBA7) [MIM:612562: A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] [2] FunctionRL11_HUMAN Binds to 5S ribosomal RNA (By similarity). Required for rRNA maturation and formation of the 60S ribosomal subunits. Promotes nucleolar location of PML (By similarity).[3] Publication Abstract from PubMedThe central region of MDM2 is critical for p53 activation and tumor suppression. Upon ribosomal stress, this region is bound by ribosomal proteins, particularly ribosomal protein L11 (RPL11), leading to MDM2 inactivation and subsequent p53 activation. Here, we solved the complex structure of human MDM2-RPL11 at 2.4 A. MDM2 extensively interacts with RPL11 through an acidic domain and two zinc fingers. Formation of the MDM2-RPL11 complex induces substantial conformational changes in both proteins. RPL11, unable to bind MDM2 mutants, fails to induce the activation of p53 in cells. MDM2 mimics 28S rRNA binding to RPL11. The C4 zinc finger determines RPL11 binding to MDM2 but not its homolog, MDMX. Our results highlight the essential role of the RPL11-MDM2 interaction in p53 activation and tumor suppression and provide a structural basis for potential new anti-tumor drug development. Structure of human MDM2 complexed with RPL11 reveals the molecular basis of p53 activation.,Zheng J, Lang Y, Zhang Q, Cui D, Sun H, Jiang L, Chen Z, Zhang R, Gao Y, Tian W, Wu W, Tang J, Chen Z Genes Dev. 2015 Jul 15;29(14):1524-34. doi: 10.1101/gad.261792.115. PMID:26220995[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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