SMN Tudor domain structure and its interaction with the Sm proteins

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 nu clear 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 th e SMN Tudor domain prevents Sm binding. Here, we have determined the three- dimensional structure of the Tudor domain of human SMN. The structure exhib its a conserved negatively charged surface that is shown to interact with t he C-terminal Arg and Gly-rich tails of Sm proteins. The E134K mutation doe s not disrupt the Tudor structure but affects the charge distribution withi n this binding site. An intriguing structural similarity between the Tudor domain and the Sm proteins suggests the presence of an additional binding i nterface that resembles that in hetero-oligomeric complexes of Sm proteins. Our data provide a structural basis for a molecular defect underlying SMA.