2L9N

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

2L9N の概要

• エントリーDOI: 10.2210/pdb2l9n/pdb
• NMR情報: BMRB: 17479
• 分子名称: Ribosome maturation protein SBDS (1 entity in total)
• 機能のキーワード: rna binding protein
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm: Q9Y3A5
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 28957.73

構造登録者

Hilcenko, C.,Freund, S.M.V.,Warren, A.J. (登録日: 2011-02-21, 公開日: 2011-05-11, 最終更新日: 2024-05-15)

主引用文献

Finch, A.J.,Hilcenko, C.,Basse, N.,Drynan, L.F.,Goyenechea, B.,Menne, T.F.,Gonzalez Fernandez, A.,Simpson, P.,D'Santos, C.S.,Arends, M.J.,Donadieu, J.,Bellanne-Chantelot, C.,Costanzo, M.,Boone, C.,McKenzie, A.N.,Freund, S.M.,Warren, A.J.
Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome.
Genes Dev., 25:917-929, 2011

PubMed Abstract: 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.

PubMed: 21536732
DOI: 10.1101/gad.623011

実験手法

SOLUTION NMR