1mhn

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spinqualitylabelsall models 1mhn, resolution 1.8Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

High resolution crystal structure of the SMN Tudor domain

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The SMN protein, which is linked to spinal muscular atrophy (SMA), plays, an important role in the assembly of the spliceosomal small nuclear, ribonucleoprotein complexes. This function requires binding of SMN to the, arginine-glycine (RG) rich C-terminal tails of the Sm proteins, which, contain symmetrically dimethylated arginine residues (sDMA) in vivo. Using, NMR titrations, we show that the SMN Tudor domain recognizes these sDMAs, in the methylated RG repeats. Upon complex formation a cluster of, conserved aromatic residues in the SMN Tudor domain interacts with the, sDMA methyl groups. We present two high resolution structures of the, uncomplexed SMN Tudor domain, a 1.8A crystal structure and an NMR, structure that has been refined against a large number of backbone and, side-chain residual dipolar couplings. The backbone conformation of both, structures is very similar, however, differences are observed for the, cluster of conserved aromatic side-chains in the sDMA binding pocket. In, order to validate these variations we introduce a novel application of, residual dipolar couplings for aromatic rings. We show that structural, information can be derived from aromatic ring residual dipolar couplings, even in the presence of internal motions such as ring flipping. These, residual dipolar couplings and ring current shifts independently confirm, that the SMN Tudor domain adopts two different conformations in the sDMA, binding pocket. The observed structural variations may play a role for the, recognition of sDMAs.

Disease

Known diseases associated with this structure: Spinal muscular atrophy-1 OMIM:[600354], Spinal muscular atrophy-2 OMIM:[600354], Spinal muscular atrophy-3 OMIM:[600354], Spinal muscular atrophy-4 OMIM:[600354]

About this Structure

1MHN is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

High-resolution X-ray and NMR structures of the SMN Tudor domain: conformational variation in the binding site for symmetrically dimethylated arginine residues., Sprangers R, Groves MR, Sinning I, Sattler M, J Mol Biol. 2003 Mar 21;327(2):507-20. PMID:12628254

Page seeded by OCA on Fri Feb 15 16:24:21 2008