SMN tudor domain structure and its interaction with the Sm proteins

Nat Struct Biol. 2001 Jan;8(1):27-31. doi: 10.1038/83014.


Spinal muscular atrophy (SMA) is a common motor neuron disease that results from mutations in the Survival of Motor Neuron (SMN) gene. The SMN protein plays a crucial role in the assembly of spliceosomal uridine-rich small nuclear ribonucleoprotein (U snRNP) complexes via binding to the spliceosomal Sm core proteins. SMN contains a central Tudor domain that facilitates the SMN-Sm protein interaction. A SMA-causing point mutation (E134K) within the SMN Tudor domain prevents Sm binding. Here, we have determined the three-dimensional structure of the Tudor domain of human SMN. The structure exhibits a conserved negatively charged surface that is shown to interact with the C-terminal Arg and Gly-rich tails of Sm proteins. The E134K mutation does not disrupt the Tudor structure but affects the charge distribution within this binding site. An intriguing structural similarity between the Tudor domain and the Sm proteins suggests the presence of an additional binding interface that resembles that in hetero-oligomeric complexes of Sm proteins. Our data provide a structural basis for a molecular defect underlying SMA.

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Binding Sites
  • Cyclic AMP Response Element-Binding Protein
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Muscular Atrophy, Spinal / metabolism
  • Mutation
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / metabolism*
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Binding
  • Protein Folding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear / metabolism*
  • SMN Complex Proteins
  • Sequence Alignment
  • Static Electricity


  • Cyclic AMP Response Element-Binding Protein
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Ribonucleoproteins, Small Nuclear
  • SMN Complex Proteins

Associated data

  • PDB/1G5V