2KDO

Structure of the human Shwachman-Bodian-Diamond syndrome protein, SBDS

Summary for 2KDO

• Entry DOI: 10.2210/pdb2kdo/pdb
• NMR Information: BMRB: 16119
• Descriptor: Ribosome maturation protein SBDS (1 entity in total)
• Functional Keywords: sbds protein, nmr protein structure, rna-interacting protein, disease mutation, phosphoprotein, ribosome biogenesis, rna binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 29008.80

Authors

de Oliveira, J.F.,Sforca, M.L.,Blumenschein, T.,Guimaraes, B.G.,Zanchin, N.I.T.,Zeri, A.C. (deposition date: 2009-01-14, release date: 2010-01-19, Last modification date: 2024-05-08)

Primary citation

de Oliveira, J.F.,Sforca, M.L.,Blumenschein, T.M.,Goldfeder, M.B.,Guimaraes, B.G.,Oliveira, C.C.,Zanchin, N.I.,Zeri, A.C.
Structure, dynamics, and RNA interaction analysis of the human SBDS protein.
J.Mol.Biol., 396:1053-1069, 2010

PubMed Abstract: Shwachman-Bodian-Diamond syndrome is an autosomal recessive genetic syndrome with pleiotropic phenotypes, including pancreatic deficiencies, bone marrow dysfunctions with increased risk of myelodysplasia or leukemia, and skeletal abnormalities. This syndrome has been associated with mutations in the SBDS gene, which encodes a conserved protein showing orthologs in Archaea and eukaryotes. The Shwachman-Bodian-Diamond syndrome pleiotropic phenotypes may be an indication of different cell type requirements for a fully functional SBDS protein. RNA-binding activity has been predicted for archaeal and yeast SBDS orthologs, with the latter also being implicated in ribosome biogenesis. However, full-length SBDS orthologs function in a species-specific manner, indicating that the knowledge obtained from model systems may be of limited use in understanding major unresolved issues regarding SBDS function, namely, the effect of mutations in human SBDS on its biochemical function and the specificity of RNA interaction. We determined the solution structure and backbone dynamics of the human SBDS protein and describe its RNA binding site using NMR spectroscopy. Similarly to the crystal structures of Archaea, the overall structure of human SBDS comprises three well-folded domains. However, significant conformational exchange was observed in NMR dynamics experiments for the flexible linker between the N-terminal domain and the central domain, and these experiments also reflect the relative motions of the domains. RNA titrations monitored by heteronuclear correlation experiments and chemical shift mapping analysis identified a classic RNA binding site at the N-terminal FYSH (fungal, Yhr087wp, Shwachman) domain that concentrates most of the mutations described for the human SBDS.

PubMed: 20053358
DOI: 10.1016/j.jmb.2009.12.039

Experimental method

SOLUTION NMR