2leh

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Solution structure of the core SMN-Gemin2 complex

Structural highlights

2leh is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Solution NMR
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GEMI2_HUMAN The SMN complex plays a catalyst role in the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. Thereby, plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP. In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. Dissociation by the SMN complex of CLNS1A from the trapped Sm proteins and their transfer to an SMN-Sm complex triggers the assembly of core snRNPs and their transport to the nucleus.[1] [2]

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[3]

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

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References

  1. ↑ Chari A, Golas MM, Klingenhager M, Neuenkirchen N, Sander B, Englbrecht C, Sickmann A, Stark H, Fischer U. An assembly chaperone collaborates with the SMN complex to generate spliceosomal SnRNPs. Cell. 2008 Oct 31;135(3):497-509. doi: 10.1016/j.cell.2008.09.020. PMID:18984161 doi:http://dx.doi.org/10.1016/j.cell.2008.09.020
  2. ↑ Liu Q, Fischer U, Wang F, Dreyfuss G. The spinal muscular atrophy disease gene product, SMN, and its associated protein SIP1 are in a complex with spliceosomal snRNP proteins. Cell. 1997 Sep 19;90(6):1013-21. PMID:9323129
  3. ↑ Sarachan KL, Valentine KG, Gupta K, Moorman VR, Gledhill Jr JM, Bernens M, Tommos C, Wand AJ, Van Duyne GD. Solution structure of the core SMN-Gemin2 complex. Biochem J. 2012 May 21. PMID:22607171 doi:10.1042/BJ20120241

Contents


PDB ID 2leh

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