SMN tudor domain structure and its interaction with the Sm proteins

Philipp Selenko, Remco Sprangers, Gunter Stier, Dirk Bühler, Utz Fischer, Michael Sattler

Research output: Contribution to journalArticlepeer-review

274 Scopus citations

Abstract

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 rule 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.

Original languageEnglish
Pages (from-to)27-31
Number of pages5
JournalNature Structural Biology
Volume8
Issue number1
DOIs
StatePublished - 2001
Externally publishedYes

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