title: Conformational flexibility and molecular interactions of an archaeal homologue of the Shwachman-Bodian-Diamond syndrome protein.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: York Structural Biology Laboratory, Chemistry Department, University of York, York, YO10 5YW, UK. clng@mrc-lmb.cam.ac.uk
authors.forename: C Leong
authors.initials: CL
authors.lastname: Ng
authors.forename: David G
authors.initials: DG
authors.lastname: Waterman
authors.forename: Eugene V
authors.initials: EV
authors.lastname: Koonin
authors.forename: Alison D
authors.initials: AD
authors.lastname: Walters
authors.forename: James P J
authors.initials: JP
authors.lastname: Chong
authors.forename: Michail N
authors.initials: MN
authors.lastname: Isupov
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Lebedev
authors.forename: David H J
authors.initials: DH
authors.lastname: Bunka
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stockley
authors.forename: Miguel
authors.initials: M
authors.lastname: Ortiz-Lombardía
authors.forename: Alfred A
authors.initials: AA
authors.lastname: Antson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019843:Archaeal Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D017013:Methanobacteriaceae / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012269:Ribosomal Proteins / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D019843:Archaeal Proteins; D011506:Proteins; D012269:Ribosomal Proteins; C470521:SBDS protein, human; D012313:RNA