Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein

Chyan Leong Ng, David G. Waterman, Eugene V. Koonin, Alison D. Walters, James Pj Chong, Michail N. Isupov, Andrey A. Lebedev, David Hj Bunka, Peter G. Stockley, Miguel Ortiz-Lombardía, Alfred A. Antson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background. Defects in the human Shwachman-Bodian-Diamond syndrome (SBDS) protein-coding gene lead to the autosomal recessive disorder characterised by bone marrow dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. This protein is highly conserved in eukaryotes and archaea but is not found in bacteria. Although genomic and biophysical studies have suggested involvement of this protein in RNA metabolism and in ribosome biogenesis, its interacting partners remain largely unknown. Results. We determined the crystal structure of the SBDS orthologue from Methanothermobacter thermautotrophicus (mthSBDS). This structure shows that SBDS proteins are highly flexible, with the N-terminal FYSH domain and the C-terminal ferredoxin-like domain capable of undergoing substantial rotational adjustments with respect to the central domain. Affinity chromatography identified several proteins from the large ribosomal subunit as possible interacting partners of mthSBDS. Moreover, SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments, combined with electrophoretic mobility shift assays (EMSA) suggest that mthSBDS does not interact with RNA molecules in a sequence specific manner. Conclusion. It is suggested that functional interactions of SBDS proteins with their partners could be facilitated by rotational adjustments of the N-terminal and the C-terminal domains with respect to the central domain. Examination of the SBDS protein structure and domain movements together with its possible interaction with large ribosomal subunit proteins suggest that these proteins could participate in ribosome function.

Original languageEnglish
Article number32
JournalBMC Structural Biology
Volume9
DOIs
Publication statusPublished - 2009
Externally publishedYes

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Large Ribosome Subunits
Proteins
Ribosomes
Methanobacteriaceae
SELEX Aptamer Technique
RNA
Exocrine Pancreatic Insufficiency
Ferredoxins
Ribosomal Proteins
Archaea
Electrophoretic Mobility Shift Assay
Eukaryota
Affinity Chromatography
Shwachman syndrome
Bone Marrow
Bacteria
Genes

ASJC Scopus subject areas

  • Structural Biology

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Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein. / Ng, Chyan Leong; Waterman, David G.; Koonin, Eugene V.; Walters, Alison D.; Chong, James Pj; Isupov, Michail N.; Lebedev, Andrey A.; Bunka, David Hj; Stockley, Peter G.; Ortiz-Lombardía, Miguel; Antson, Alfred A.

In: BMC Structural Biology, Vol. 9, 32, 2009.

Research output: Contribution to journalArticle

Ng, CL, Waterman, DG, Koonin, EV, Walters, AD, Chong, JP, Isupov, MN, Lebedev, AA, Bunka, DH, Stockley, PG, Ortiz-Lombardía, M & Antson, AA 2009, 'Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein', BMC Structural Biology, vol. 9, 32. https://doi.org/10.1186/1472-6807-9-32
Ng, Chyan Leong ; Waterman, David G. ; Koonin, Eugene V. ; Walters, Alison D. ; Chong, James Pj ; Isupov, Michail N. ; Lebedev, Andrey A. ; Bunka, David Hj ; Stockley, Peter G. ; Ortiz-Lombardía, Miguel ; Antson, Alfred A. / Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein. In: BMC Structural Biology. 2009 ; Vol. 9.
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abstract = "Background. Defects in the human Shwachman-Bodian-Diamond syndrome (SBDS) protein-coding gene lead to the autosomal recessive disorder characterised by bone marrow dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. This protein is highly conserved in eukaryotes and archaea but is not found in bacteria. Although genomic and biophysical studies have suggested involvement of this protein in RNA metabolism and in ribosome biogenesis, its interacting partners remain largely unknown. Results. We determined the crystal structure of the SBDS orthologue from Methanothermobacter thermautotrophicus (mthSBDS). This structure shows that SBDS proteins are highly flexible, with the N-terminal FYSH domain and the C-terminal ferredoxin-like domain capable of undergoing substantial rotational adjustments with respect to the central domain. Affinity chromatography identified several proteins from the large ribosomal subunit as possible interacting partners of mthSBDS. Moreover, SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments, combined with electrophoretic mobility shift assays (EMSA) suggest that mthSBDS does not interact with RNA molecules in a sequence specific manner. Conclusion. It is suggested that functional interactions of SBDS proteins with their partners could be facilitated by rotational adjustments of the N-terminal and the C-terminal domains with respect to the central domain. Examination of the SBDS protein structure and domain movements together with its possible interaction with large ribosomal subunit proteins suggest that these proteins could participate in ribosome function.",
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AU - Walters, Alison D.

AU - Chong, James Pj

AU - Isupov, Michail N.

AU - Lebedev, Andrey A.

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AU - Ortiz-Lombardía, Miguel

AU - Antson, Alfred A.

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N2 - Background. Defects in the human Shwachman-Bodian-Diamond syndrome (SBDS) protein-coding gene lead to the autosomal recessive disorder characterised by bone marrow dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. This protein is highly conserved in eukaryotes and archaea but is not found in bacteria. Although genomic and biophysical studies have suggested involvement of this protein in RNA metabolism and in ribosome biogenesis, its interacting partners remain largely unknown. Results. We determined the crystal structure of the SBDS orthologue from Methanothermobacter thermautotrophicus (mthSBDS). This structure shows that SBDS proteins are highly flexible, with the N-terminal FYSH domain and the C-terminal ferredoxin-like domain capable of undergoing substantial rotational adjustments with respect to the central domain. Affinity chromatography identified several proteins from the large ribosomal subunit as possible interacting partners of mthSBDS. Moreover, SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments, combined with electrophoretic mobility shift assays (EMSA) suggest that mthSBDS does not interact with RNA molecules in a sequence specific manner. Conclusion. It is suggested that functional interactions of SBDS proteins with their partners could be facilitated by rotational adjustments of the N-terminal and the C-terminal domains with respect to the central domain. Examination of the SBDS protein structure and domain movements together with its possible interaction with large ribosomal subunit proteins suggest that these proteins could participate in ribosome function.

AB - Background. Defects in the human Shwachman-Bodian-Diamond syndrome (SBDS) protein-coding gene lead to the autosomal recessive disorder characterised by bone marrow dysfunction, exocrine pancreatic insufficiency and skeletal abnormalities. This protein is highly conserved in eukaryotes and archaea but is not found in bacteria. Although genomic and biophysical studies have suggested involvement of this protein in RNA metabolism and in ribosome biogenesis, its interacting partners remain largely unknown. Results. We determined the crystal structure of the SBDS orthologue from Methanothermobacter thermautotrophicus (mthSBDS). This structure shows that SBDS proteins are highly flexible, with the N-terminal FYSH domain and the C-terminal ferredoxin-like domain capable of undergoing substantial rotational adjustments with respect to the central domain. Affinity chromatography identified several proteins from the large ribosomal subunit as possible interacting partners of mthSBDS. Moreover, SELEX (Systematic Evolution of Ligands by EXponential enrichment) experiments, combined with electrophoretic mobility shift assays (EMSA) suggest that mthSBDS does not interact with RNA molecules in a sequence specific manner. Conclusion. It is suggested that functional interactions of SBDS proteins with their partners could be facilitated by rotational adjustments of the N-terminal and the C-terminal domains with respect to the central domain. Examination of the SBDS protein structure and domain movements together with its possible interaction with large ribosomal subunit proteins suggest that these proteins could participate in ribosome function.

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