| Structural highlights
Disease
RS19_HUMAN Blackfan-Diamond disease. Diamond-Blackfan anemia 1 (DBA1) [MIM:105650: 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 developing leukemia. 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] [3] [4] [5] [6] [7] [REFERENCE:18]
Function
RS19_HUMAN Required for pre-rRNA processing and maturation of 40S ribosomal subunits.[8]
Publication Abstract from PubMed
The repertoire of the density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein was recently expanded to include translational control of a specific set of cancer-related mRNAs. DENR and MCT-1 form the heterodimer, which binds to the ribosome and operates at both translation initiation and reinitiation steps, though by a mechanism that is yet unclear. Here, we determined the crystal structure of the human small ribosomal subunit in complex with DENR-MCT-1. The structure reveals the location of the DENR-MCT-1 dimer bound to the small ribosomal subunit. The binding site of the C-terminal domain of DENR on the ribosome has a striking similarity with those of canonical initiation factor 1 (eIF1), which controls the fidelity of translation initiation and scanning. Our findings elucidate how the DENR-MCT-1 dimer interacts with the ribosome and have functional implications for the mechanism of unconventional translation initiation and reinitiation.
Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1.,Lomakin IB, Stolboushkina EA, Vaidya AT, Zhao C, Garber MB, Dmitriev SE, Steitz TA Cell Rep. 2017 Jul 18;20(3):521-528. doi: 10.1016/j.celrep.2017.06.025. PMID:28723557[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Angelini M, Cannata S, Mercaldo V, Gibello L, Santoro C, Dianzani I, Loreni F. Missense mutations associated with Diamond-Blackfan anemia affect the assembly of ribosomal protein S19 into the ribosome. Hum Mol Genet. 2007 Jul 15;16(14):1720-7. Epub 2007 May 20. PMID:17517689 doi:ddm120
- ↑ Da Costa L, Tchernia G, Gascard P, Lo A, Meerpohl J, Niemeyer C, Chasis JA, Fixler J, Mohandas N. Nucleolar localization of RPS19 protein in normal cells and mislocalization due to mutations in the nucleolar localization signals in 2 Diamond-Blackfan anemia patients: potential insights into pathophysiology. Blood. 2003 Jun 15;101(12):5039-45. Epub 2003 Feb 13. PMID:12586610 doi:10.1182/blood-2002-12-3878
- ↑ Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet. 1999 Feb;21(2):169-75. PMID:9988267 doi:10.1038/5951
- ↑ Willig TN, Draptchinskaia N, Dianzani I, Ball S, Niemeyer C, Ramenghi U, Orfali K, Gustavsson P, Garelli E, Brusco A, Tiemann C, Perignon JL, Bouchier C, Cicchiello L, Dahl N, Mohandas N, Tchernia G. Mutations in ribosomal protein S19 gene and diamond blackfan anemia: wide variations in phenotypic expression. Blood. 1999 Dec 15;94(12):4294-306. PMID:10590074
- ↑ Ramenghi U, Campagnoli MF, Garelli E, Carando A, Brusco A, Bagnara GP, Strippoli P, Izzi GC, Brandalise S, Riccardi R, Dianzani I. Diamond-Blackfan anemia: report of seven further mutations in the RPS19 gene and evidence of mutation heterogeneity in the Italian population. Blood Cells Mol Dis. 2000 Oct;26(5):417-22. PMID:11112378 doi:10.1006/bcmd.2000.0324
- ↑ Proust A, Da Costa L, Rince P, Landois A, Tamary H, Zaizov R, Tchernia G, Delaunay J. Ten novel Diamond-Blackfan anemia mutations and three polymorphisms within the rps19 gene. Hematol J. 2003;4(2):132-6. PMID:12750732 doi:10.1038/sj.thj.6200230
- ↑ Gazda HT, Zhong R, Long L, Niewiadomska E, Lipton JM, Ploszynska A, Zaucha JM, Vlachos A, Atsidaftos E, Viskochil DH, Niemeyer CM, Meerpohl JJ, Rokicka-Milewska R, Pospisilova D, Wiktor-Jedrzejczak W, Nathan DG, Beggs AH, Sieff CA. RNA and protein evidence for haplo-insufficiency in Diamond-Blackfan anaemia patients with RPS19 mutations. Br J Haematol. 2004 Oct;127(1):105-13. PMID:15384984 doi:10.1111/j.1365-2141.2004.05152.x
- ↑ Flygare J, Aspesi A, Bailey JC, Miyake K, Caffrey JM, Karlsson S, Ellis SR. Human RPS19, the gene mutated in Diamond-Blackfan anemia, encodes a ribosomal protein required for the maturation of 40S ribosomal subunits. Blood. 2007 Feb 1;109(3):980-6. Epub 2006 Sep 21. PMID:16990592 doi:blood-2006-07-038232
- ↑ Lomakin IB, Stolboushkina EA, Vaidya AT, Zhao C, Garber MB, Dmitriev SE, Steitz TA. Crystal Structure of the Human Ribosome in Complex with DENR-MCT-1. Cell Rep. 2017 Jul 18;20(3):521-528. doi: 10.1016/j.celrep.2017.06.025. PMID:28723557 doi:http://dx.doi.org/10.1016/j.celrep.2017.06.025
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