SBDS explained
Ribosome maturation protein SBDS is a protein that in humans is encoded by the SBDS gene.[1] An alternative transcript has been described, but its biological nature has not been determined. This gene has a closely linked pseudogene that is distally located.[2] This gene encodes a member of a highly conserved protein family that exists in all archaea and eukaryotes.
Function
The encoded protein plays an essential role in ribosome biogenesis. SBDS interacts with elongation factor-like GTPase 1 (Efl1) to disassociate eukaryotic initiation factor 6 (eIF6) from the late cytoplasmic pre-60S ribosomal subunit allowing assembly of the 80S. Dynamic rotation of the SBDS protein in the ribosomal P site is coupled to a conformational switch in EFL1 that promotes eIF6 displacement through competition for an overlapping binding site on the 60S ribosomal subunit.[3] Yeast SBDS ortholog, Sdo1, functions within a pathway containing Efl1 to facilitate the release and recycling of the nucleolar shuttling factor Tif6 (yeast eIF6 ortholog) from late cytoplasmic pre-60S ribosomal subunit.[4] Knockdown of SBDS expression results in increased apoptosis in erythroid cells undergoing differentiation due to elevated ROS levels.[5] Hence SBDS is critical for normal erythropoiesis.[6]
This family is highly conserved in species ranging from archaea to vertebrates and plants. The family contains several Shwachman-Bodian-Diamond syndrome (SBDS) proteins from both mouse and humans. Shwachman-Diamond syndrome is an autosomal recessive disorder with clinical features that include pancreatic exocrine insufficiency, haematological dysfunction and skeletal abnormalities. Members of this family play a role in RNA metabolism.[1] [7]
A number of uncharacterised hydrophilic proteins of about 30 kDa share regions of similarity. These include,
- Mouse protein 22A3.
- Saccharomyces cerevisiae chromosome XII hypothetical protein YLR022c.
- Caenorhabditis elegans hypothetical protein W06E11.4.
- Methanococcus jannaschii hypothetical protein MJ0592.
This particular protein sequence is highly conserved in species ranging from archaea to vertebrates and plants.[1]
Structure
The SBDS protein contains three domains, an N-terminal conserved FYSH domain, central helical domain and C-terminal domain containing an RNA-binding motif.[5]
N-terminal domain
| Align: | left |
| Symbol: | SBDS |
| SBDS protein N-terminal domain |
| Pfam: | PF01172 |
| Interpro: | IPR019783 |
| Prosite: | PDOC00974 |
| Scop: | 1nyn |
This protein domain appears to be very important, since mutations in this domain are usually the cause of Shwachman-Bodian-Diamond syndrome. It shares distant structural and sequence homology to a protein named YHR087W found in the yeast Saccharomyces cerevisiae. The protein YHR087W is involved in RNA metabolism, so it is probable that the SBDS N-terminal domain has the same function.
The N-terminal domains contains a novel mixed alphabeta fold, four beta-strands, and four alpha-helices arranged as a three beta stranded anti-parallel-sheet.
Central domain
The function of this protein domain has been difficult to elucidate. It is possible that it has a role in binding to DNA or RNA. Protein binding to form a protein complex is also another possibility. It has been difficult to infer the function from the structure since this particular domain structure is found in archea.
This domain contains a very common structure, the winged helix-turn-helix.
C-terminal domain
In molecular biology, the SBDS C-terminal protein domain is highly conserved in species ranging from archaea to vertebrates and plants.[1]
Members of this family are thought to play a role in RNA metabolism. However, its precise function remains to be elucidated. Furthermore, its structure makes it very difficult to predict the protein domain's function.
The structure of the C-terminal domain contains a ferredoxin-like fold[8] This structure has a four-stranded beta-sheet with two helices on one side.
Clinical significance
Mutations within this gene are associated with Shwachman-Bodian-Diamond syndrome. The two most common mutations associated with this syndrome are at positions 183–184 (TA→CT) resulting in a premature stop-codon (K62X) and a frameshift mutation at position 258 (2T→C) resulting in a stopcodon (C84fsX3).[5]
Further reading
- Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W . Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics . Genome Research . 10 . 5 . 703–13 . May 2000 . 10810093 . 310876 . 10.1101/gr.10.5.703 .
- Popovic M, Goobie S, Morrison J, Ellis L, Ehtesham N, Richards N, Boocock G, Durie PR, Rommens JM . 6 . Fine mapping of the locus for Shwachman-Diamond syndrome at 7q11, identification of shared disease haplotypes, and exclusion of TPST1 as a candidate gene . European Journal of Human Genetics . 10 . 4 . 250–8 . April 2002 . 12032733 . 10.1038/sj.ejhg.5200798 . 12667823 . free .
- Nakashima E, Mabuchi A, Makita Y, Masuno M, Ohashi H, Nishimura G, Ikegawa S . Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome . Human Genetics . 114 . 4 . 345–8 . March 2004 . 14749921 . 10.1007/s00439-004-1081-2 . 30492406 .
- Woloszynek JR, Rothbaum RJ, Rawls AS, Minx PJ, Wilson RK, Mason PJ, Bessler M, Link DC . 6 . Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome . Blood . 104 . 12 . 3588–90 . December 2004 . 15284109 . 10.1182/blood-2004-04-1516 . 43717208 .
- Andersen JS, Lam YW, Leung AK, Ong SE, Lyon CE, Lamond AI, Mann M . Nucleolar proteome dynamics . Nature . 433 . 7021 . 77–83 . January 2005 . 15635413 . 10.1038/nature03207 . 2005Natur.433...77A . 4344740 .
- Kuijpers TW, Alders M, Tool AT, Mellink C, Roos D, Hennekam RC . Hematologic abnormalities in Shwachman Diamond syndrome: lack of genotype-phenotype relationship . Blood . 106 . 1 . 356–61 . July 2005 . 15769891 . 10.1182/blood-2004-11-4371 . free .
- Austin KM, Leary RJ, Shimamura A . The Shwachman-Diamond SBDS protein localizes to the nucleolus . Blood . 106 . 4 . 1253–8 . August 2005 . 15860664 . 1895203 . 10.1182/blood-2005-02-0807 .
- Kawakami T, Mitsui T, Kanai M, Shirahata E, Sendo D, Kanno M, Noro M, Endoh M, Hama A, Tono C, Ito E, Tsuchiya S, Igarashi Y, Abukawa D, Hayasaka K . 6 . Genetic analysis of Shwachman-Diamond syndrome: phenotypic heterogeneity in patients carrying identical SBDS mutations . The Tohoku Journal of Experimental Medicine . 206 . 3 . 253–9 . July 2005 . 15942154 . 10.1620/tjem.206.253 . free .
- Boocock GR, Marit MR, Rommens JM . Phylogeny, sequence conservation, and functional complementation of the SBDS protein family . Genomics . 87 . 6 . 758–71 . June 2006 . 16529906 . 10.1016/j.ygeno.2006.01.010 .
- Erdos M, Alapi K, Balogh I, Oroszlán G, Rákóczi E, Sümegi J, Maródi L . Severe Shwachman-Diamond syndrome phenotype caused by compound heterozygous missense mutations in the SBDS gene . Experimental Hematology . 34 . 11 . 1517–21 . November 2006 . 17046571 . 10.1016/j.exphem.2006.06.009 . free .
- Nishimura G, Nakashima E, Hirose Y, Cole T, Cox P, Cohn DH, Rimoin DL, Lachman RS, Miyamoto Y, Kerr B, Unger S, Ohashi H, Superti-Furga A, Ikegawa S . 6 . The Shwachman-Bodian-Diamond syndrome gene mutations cause a neonatal form of spondylometaphysial dysplasia (SMD) resembling SMD Sedaghatian type . Journal of Medical Genetics . 44 . 4 . e73 . April 2007 . 17400792 . 2598034 . 10.1136/jmg.2006.043869 .
- Calado RT, Graf SA, Wilkerson KL, Kajigaya S, Ancliff PJ, Dror Y, Chanock SJ, Lansdorp PM, Young NS . 6 . Mutations in the SBDS gene in acquired aplastic anemia . Blood . 110 . 4 . 1141–6 . August 2007 . 17478638 . 1939897 . 10.1182/blood-2007-03-080044 .
- Wang Y, Yagasaki H, Hama A, Nishio N, Takahashi Y, Kojima S . Mutation of SBDS and SH2D1A is not associated with aplastic anemia in Japanese children . Haematologica . 92 . 11 . 1573 . November 2007 . 18024409 . 10.3324/haematol.11568 . free .
External links
Notes and References
- Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM . Mutations in SBDS are associated with Shwachman-Diamond syndrome . Nature Genetics . 33 . 1 . 97–101 . January 2003 . 12496757 . 10.1038/ng1062 . 5091627 .
- Web site: Entrez Gene: SBDS Shwachman-Bodian-Diamond syndrome.
- Weis F, Giudice E, Churcher M, Jin L, Hilcenko C, Wong CC, Traynor D, Kay RR, Warren AJ . 6 . Mechanism of eIF6 release from the nascent 60S ribosomal subunit . Nature Structural & Molecular Biology . 22 . 11 . 914–9 . November 2015 . 26479198 . 4871238 . 10.1038/nsmb.3112 .
- Menne TF, Goyenechea B, Sánchez-Puig N, Wong CC, Tonkin LM, Ancliff PJ, Brost RL, Costanzo M, Boone C, Warren AJ . 6 . The Shwachman-Bodian-Diamond syndrome protein mediates translational activation of ribosomes in yeast . Nature Genetics . 39 . 4 . 486–95 . April 2007 . 17353896 . 10.1038/ng1994 . Nuria . Beatriz . Louise M. . Chi C. . 8076230 .
- Orelio C, van der Sluis RM, Verkuijlen P, Nethe M, Hordijk PL, van den Berg TK, Kuijpers TW . Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome . PLOS ONE . 6 . 6 . e20727 . 2011 . 21695142 . 3113850 . 10.1371/journal.pone.0020727 . 2011PLoSO...620727O . free .
- Sen S, Wang H, Nghiem CL, Zhou K, Yau J, Tailor CS, Irwin MS, Dror Y . 6 . The ribosome-related protein, SBDS, is critical for normal erythropoiesis . Blood . 118 . 24 . 6407–17 . December 2011 . 21963601 . 10.1182/blood-2011-02-335190 . 16823156 .
- Savchenko A, Krogan N, Cort JR, Evdokimova E, Lew JM, Yee AA, Sánchez-Pulido L, Andrade MA, Bochkarev A, Watson JD, Kennedy MA, Greenblatt J, Hughes T, Arrowsmith CH, Rommens JM, Edwards AM . 6 . The Shwachman-Bodian-Diamond syndrome protein family is involved in RNA metabolism . The Journal of Biological Chemistry . 280 . 19 . 19213–20 . May 2005 . 15701634 . 10.1074/jbc.M414421200 . free .
- Shammas C, Menne TF, Hilcenko C, Michell SR, Goyenechea B, Boocock GR, Durie PR, Rommens JM, Warren AJ . 6 . Structural and mutational analysis of the SBDS protein family. Insight into the leukemia-associated Shwachman-Diamond Syndrome . The Journal of Biological Chemistry . 280 . 19 . 19221–9 . May 2005 . 15701631 . 10.1074/jbc.M414656200 . free .
