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PDBsum entry 2kdo
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RNA binding protein
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PDB id
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2kdo
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References listed in PDB file
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Key reference
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Title
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Structure, Dynamics, And RNA interaction analysis of the human sbds protein.
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Authors
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J.F.De oliveira,
M.L.Sforça,
T.M.Blumenschein,
M.B.Goldfeder,
B.G.Guimarães,
C.C.Oliveira,
N.I.Zanchin,
A.C.Zeri.
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Ref.
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J Mol Biol, 2010,
396,
1053-1069.
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PubMed id
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Abstract
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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.
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