| Structural highlights
Function
[SPF30_HUMAN] Necessary for spliceosome assembly. Overexpression causes apoptosis.[1] [2] [3]
Publication Abstract from PubMed
Arginine dimethylation plays critical roles in the assembly of ribonucleoprotein complexes in pre-mRNA splicing and piRNA pathways. We report solution structures of SMN and SPF30 Tudor domains bound to symmetric and asymmetric dimethylated arginine (DMA) that is inherent in the RNP complexes. An aromatic cage in the Tudor domain mediates dimethylarginine recognition by electrostatic stabilization through cation-pi interactions. Distinct from extended Tudor domains, dimethylarginine binding by the SMN and SPF30 Tudor domains is independent of proximal residues in the ligand. Yet, enhanced micromolar affinities are obtained by external cooperativity when multiple methylation marks are presented in arginine- and glycine-rich peptide ligands. A hydrogen bond network in the SMN Tudor domain, including Glu134 and a tyrosine hydroxyl of the aromatic cage, enhances cation-pi interactions and is impaired by a mutation causing an E134K substitution associated with spinal muscular atrophy. Our structural analysis enables the design of an optimized binding pocket and the prediction of DMA binding properties of Tudor domains.
Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins.,Tripsianes K, Madl T, Machyna M, Fessas D, Englbrecht C, Fischer U, Neugebauer KM, Sattler M Nat Struct Mol Biol. 2011 Nov 20. doi: 10.1038/nsmb.2185. PMID:22101937[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Talbot K, Miguel-Aliaga I, Mohaghegh P, Ponting CP, Davies KE. Characterization of a gene encoding survival motor neuron (SMN)-related protein, a constituent of the spliceosome complex. Hum Mol Genet. 1998 Dec;7(13):2149-56. PMID:9817934
- ↑ Meister G, Hannus S, Plottner O, Baars T, Hartmann E, Fakan S, Laggerbauer B, Fischer U. SMNrp is an essential pre-mRNA splicing factor required for the formation of the mature spliceosome. EMBO J. 2001 May 1;20(9):2304-14. PMID:11331595 doi:http://dx.doi.org/10.1093/emboj/20.9.2304
- ↑ Rappsilber J, Ajuh P, Lamond AI, Mann M. SPF30 is an essential human splicing factor required for assembly of the U4/U5/U6 tri-small nuclear ribonucleoprotein into the spliceosome. J Biol Chem. 2001 Aug 17;276(33):31142-50. Epub 2001 Apr 30. PMID:11331295 doi:http://dx.doi.org/10.1074/jbc.M103620200
- ↑ Tripsianes K, Madl T, Machyna M, Fessas D, Englbrecht C, Fischer U, Neugebauer KM, Sattler M. Structural basis for dimethylarginine recognition by the Tudor domains of human SMN and SPF30 proteins. Nat Struct Mol Biol. 2011 Nov 20. doi: 10.1038/nsmb.2185. PMID:22101937 doi:10.1038/nsmb.2185
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