PDBsum entry: 1g5v

Translation

PDB id: 1g5v

Contents

Protein chain

56 a.a. *

* Residue conservation analysis

PDB id:

1g5v

Name:

Translation

Title:

Solution structure of the tudor domain of the human smn protein

Structure:

Survival motor neuron protein 1. Chain: a. Fragment: tudor domain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: smn1. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Terminal his6-gst and tev cleavage site

NMR struc:

10 models

Authors:

P.Selenko,R.Sprangers,G.Stier,D.Buehler,U.Fischer,M.Sattler

Key ref:

P.Selenko et al. (2001). SMN tudor domain structure and its interaction with the Sm proteins. Nat Struct Biol, 8, 27-31. PubMed id: 11135666 DOI: 10.1038/83014

Date:

02-Nov-00 Release date: 02-May-01

Protein chain

Q16637  (SMN_HUMAN) -  Survival motor neuron protein

Seq: 294 a.a.

Struc: 56 a.a.

 Gene Ontology (GO) functional annotation 

• Biochemical function: nucleic acid binding (1 term)

DOI no: 10.1038/83014

Nat Struct Biol 8:27-31 (2001)

PubMed id: 11135666

SMN tudor domain structure and its interaction with the Sm proteins.

P.Selenko, R.Sprangers, G.Stier, D.Bühler, U.Fischer, M.Sattler.

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 role 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.

Selected figure(s)

Figure 3.
Figure 3. Mapping the Sm binding site on the Tudor domain structure. a, Results of the NMR titration using a 23-mer peptide comprising the C-terminal tail of the Sm D[1] protein added to a 0.3 mM 15N-labeled SMN Tudor domain sample. 1H,15N correlation spectra corresponding to 0, 0.1 and 0.3 mM peptide are shown in blue, green and red, respectively. b, Residues for which changes are observed during the NMR titration are colored on the surface of the Tudor domain structure. Coloring from gray to orange scales with increasing chemical shift change as indicated ( av = (( [1H])2 + ( [15N])2)1/2 , where is the chemical shift difference observed at 0 and 0.3 mM peptide). The surface on the left is in the same orientation as in Fig. 1d; the surface on the right shows a view from the back side. c, Ribbon representation in the same orientation as in (b, left). The side chains of amino acids whose amide groups experience chemical shift changes av > 35 Hz are shown. Color coding from yellow to orange is the same as in (b). d, 1H,15N correlation spectra recorded on a 0.1 mM 15N-labeled sample of the E134K mutant Tudor domain with 0 (blue), 0.1 (green) or 1 mM (red) Sm D[1] tail peptide. Minor chemical shift changes were observed only at 10-fold molar excess of the peptide, confirming that the affinity is severely reduced compared to the wild type Tudor domain.

Figure 4.
Figure 4. The Tudor domain resembles a truncated Sm fold. a, Comparison of the SMN Tudor domain structure and the Sm D[ 3] protein. Both structures share a common fold consisting of a strongly bent five-stranded -sheet. The backbone r.m.s. deviation for the superposition of 49 residues in Sm D[3] and SMN Tudor is 3 Å. The residue numbers that were superimposed between the Tudor domain and Sm D[3] are: Tudor: 91 -101, 105 -118, 120 -129, 130 -137, 140 -144; Sm D[3]: 11 -21, 24 -37, 38 -47, 57 -64, 70 -74. The circle indicates the extension of strands 3 and 4 in the Sm D[3] protein that is not observed in the fold of the Tudor domain. b, Crystal structure of the human Sm D[1]D[2] heterodimer14. The -strands that form the dimer interface ( 5 of Sm D[1] and 4 of Sm D[2]) are shown in orange. For Sm D[1], only the core domain (residues 9 -72) is shown for clarity. Strands 4 of Sm D[1] and 5 of Sm D[2], also shown in orange, are assumed to form similar interactions with neighboring Sm hetero-oligomers in the heptameric Sm core complex14.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nat Struct Biol (2001, 8, 27-31) copyright 2001.

Figures were selected by an automated process.