4A4G

Solution structure of SMN Tudor domain in complex with asymmetrically dimethylated arginine

4A4G の概要

• エントリーDOI: 10.2210/pdb4a4g/pdb
• 関連するPDBエントリー: 1G5V 1MHN 4A4E
• NMR情報: BMRB: 18007
• 分子名称: SURVIVAL MOTOR NEURON PROTEIN, NG,NG-DIMETHYL-L-ARGININE (2 entities in total)
• 機能のキーワード: rna binding protein
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q16637
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 7296.15

構造登録者

Tripsianes, K.,Madl, T.,Machyna, M.,Fessas, D.,Englbrecht, C.,Fischer, U.,Neugebauer, K.M.,Sattler, M. (登録日: 2011-10-12, 公開日: 2011-11-30, 最終更新日: 2023-11-15)

主引用文献

Tripsianes, K.,Madl, T.,Machyna, M.,Fessas, D.,Englbrecht, C.,Fischer, U.,Neugebauer, K.M.,Sattler, M.
Structural Basis for Dimethyl-Arginine Recognition by the Tudor Domains of Human Smn and Spf30 Proteins
Nat.Struct.Mol.Biol., 18:1414-, 2011

PubMed Abstract: 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-π 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-π 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.

PubMed: 22101937
DOI: 10.1038/NSMB.2185

実験手法

SOLUTION NMR