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2l9n

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Revision as of 19:31, 1 August 2018

Structure of the human Shwachman-Bodian-Diamond syndrome (SBDS) protein

Structural highlights

2l9n is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	CGI-97, SBDS (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[SBDS_HUMAN] Idiopathic aplastic anemia;Shwachman-Diamond syndrome. The disease is caused by mutations affecting the gene represented in this entry.^[1] ^[2]

Function

[SBDS_HUMAN] Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFTUD1, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation.^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Removal of the assembly factor eukaryotic initiation factor 6 (eIF6) is critical for late cytoplasmic maturation of 60S ribosomal subunits. In mammalian cells, the current model posits that eIF6 release is triggered following phosphorylation of Ser 235 by activated protein kinase C. In contrast, genetic studies in yeast indicate a requirement for the ortholog of the SBDS (Shwachman-Bodian-Diamond syndrome) gene that is mutated in the inherited leukemia predisposition disorder Shwachman-Diamond syndrome (SDS). Here, by isolating late cytoplasmic 60S ribosomal subunits from Sbds-deleted mice, we show that SBDS and the GTPase elongation factor-like 1 (EFL1) directly catalyze eIF6 removal in mammalian cells by a mechanism that requires GTP binding and hydrolysis by EFL1 but not phosphorylation of eIF6 Ser 235. Functional analysis of disease-associated missense variants reveals that the essential role of SBDS is to tightly couple GTP hydrolysis by EFL1 on the ribosome to eIF6 release. Furthermore, complementary NMR spectroscopic studies suggest unanticipated mechanistic parallels between this late step in 60S maturation and aspects of bacterial ribosome disassembly. Our findings establish a direct role for SBDS and EFL1 in catalyzing the translational activation of ribosomes in all eukaryotes, and define SDS as a ribosomopathy caused by uncoupling GTP hydrolysis from eIF6 release.

Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.,Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011
↑ Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM. Mutations in SBDS are associated with Shwachman-Diamond syndrome. Nat Genet. 2003 Jan;33(1):97-101. Epub 2002 Dec 23. PMID:12496757 doi:http://dx.doi.org/10.1038/ng1062
↑ Hesling C, Oliveira CC, Castilho BA, Zanchin NI. The Shwachman-Bodian-Diamond syndrome associated protein interacts with HsNip7 and its down-regulation affects gene expression at the transcriptional and translational levels. Exp Cell Res. 2007 Dec 10;313(20):4180-95. Epub 2007 Jul 10. PMID:17643419 doi:10.1016/j.yexcr.2007.06.024
↑ Ball HL, Zhang B, Riches JJ, Gandhi R, Li J, Rommens JM, Myers JS. Shwachman-Bodian Diamond syndrome is a multi-functional protein implicated in cellular stress responses. Hum Mol Genet. 2009 Oct 1;18(19):3684-95. doi: 10.1093/hmg/ddp316. Epub 2009 Jul , 14. PMID:19602484 doi:http://dx.doi.org/10.1093/hmg/ddp316
↑ Orelio C, Verkuijlen P, Geissler J, van den Berg TK, Kuijpers TW. SBDS expression and localization at the mitotic spindle in human myeloid progenitors. PLoS One. 2009 Sep 17;4(9):e7084. doi: 10.1371/journal.pone.0007084. PMID:19759903 doi:http://dx.doi.org/10.1371/journal.pone.0007084
↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011
↑ Finch AJ, Hilcenko C, Basse N, Drynan LF, Goyenechea B, Menne TF, Gonzalez Fernandez A, Simpson P, D'Santos CS, Arends MJ, Donadieu J, Bellanne-Chantelot C, Costanzo M, Boone C, McKenzie AN, Freund SM, Warren AJ. Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome. Genes Dev. 2011 May 1;25(9):917-29. PMID:21536732 doi:10.1101/gad.623011

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l9n"

Categories: Human | Freund, S M.V | Hilcenko, C | Warren, A J | Rna binding protein

@@ Line 1: / Line 1: @@
 ==Structure of the human Shwachman-Bodian-Diamond syndrome (SBDS) protein==
 <StructureSection load='2l9n' size='340' side='right' caption='[[2l9n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
@@ Line 4: / Line 5: @@
 <table><tr><td colspan='2'>[[2l9n]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L9N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L9N FirstGlance]. <br>
 </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CGI-97, SBDS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l9n OCA], [http://pdbe.org/2l9n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l9n RCSB], [http://www.ebi.ac.uk/pdbsum/2l9n PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2l9n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l9n OCA], [http://pdbe.org/2l9n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l9n RCSB], [http://www.ebi.ac.uk/pdbsum/2l9n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l9n ProSAT]</span></td></tr>
 </table>
 == Disease ==

2l9n

From Proteopedia

Revision as of 19:31, 1 August 2018

Structure of the human Shwachman-Bodian-Diamond syndrome (SBDS) protein

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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