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Publication Abstract from PubMed

In humans, assembly of spliceosomal snRNPs begins in the cytoplasm where the multi-protein SMN complex mediates formation of a seven-membered ring of Sm proteins onto a conserved site of the snRNA. The SMN complex contains the survival of motor neuron (SMN) protein, Gemin2, and several additional 'Gemins' that participate in snRNP biosynthesis. SMN was first identified as the product of a gene found to be deleted or mutated in patients with the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. Here, we report the solution structure of Gemin2 bound to the Gemin2-binding domain of SMN determined by NMR spectroscopy. This complex reveals the structure of Gemin2, how Gemin2 binds to SMN, and the roles of conserved SMN residues near the binding interface. Surprisingly, several conserved SMN residues, including the sites of two SMA patient mutations, are not required for binding to Gemin2. Instead, they form a conserved SMN/Gemin2 surface that may be functionally important for snRNP assembly. The SMN-Gemin2 structure explains how Gemin2 is stabilized by SMN and establishes a framework for structure-function studies to investigate snRNP biogenesis as well as biological processes involving Gemin2 that do not involve snRNP assembly.

Solution structure of the core SMN-Gemin2 complex.,Sarachan KL, Valentine KG, Gupta K, Moorman VR, Gledhill Jr JM, Bernens M, Tommos C, Wand AJ, Van Duyne GD Biochem J. 2012 May 21. PMID:22607171^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.