Open Access Highly Accessed Research article

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

C Leong Ng12, David G Waterman1, Eugene V Koonin3, Alison D Walters4, James PJ Chong4, Michail N Isupov5, Andrey A Lebedev1, David HJ Bunka6, Peter G Stockley6, Miguel Ortiz-Lombardía17* and Alfred A Antson1*

Author Affiliations

1 York Structural Biology Laboratory, Chemistry Department, University of York, York, YO10 5YW, UK

2 Structural Studies Division, MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK

3 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, USA

4 Department of Biology, University of York, York, YO10 5YW, UK

5 Henry Wellcome Building for Biocatalysis, School of Biosciences, University of Exeter, Stocker Road, Exeter, EX4 4QD, UK

6 Astbury Centre for Structural Molecular Biology, University of Leeds, Leeds, LS2 9JT, UK

7 Current address: Architécture et Fonction des Macromolécules Biologiques UMR 9068, Case 932, 163 Avenue de Luminy, 13288 Marseille cedex 9, France

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BMC Structural Biology 2009, 9:32  doi:10.1186/1472-6807-9-32

Published: 19 May 2009



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.


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.


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.