2YH0

Solution structure of the closed conformation of human U2AF65 tandem RRM1 and RRM2 domains

2YH0 の概要

• エントリーDOI: 10.2210/pdb2yh0/pdb
• 関連するPDBエントリー: 1JMT 1O0P 1OPI 1U2F 2G4B 2U2F 2YH1 2YH4
• NMR情報: BMRB: 17622
• 分子名称: SPLICING FACTOR U2AF 65 KDA SUBUNIT (1 entity in total)
• 機能のキーワード: pre-mrna splicing, transcription, rna binding protein, mrna processing
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21510.53

構造登録者

Mackereth, C.D.,Madl, T.,Simon, B.,Zanier, K.,Gasch, A.,Sattler, M. (登録日: 2011-04-26, 公開日: 2011-07-20, 最終更新日: 2024-05-15)

主引用文献

Mackereth, C.D.,Madl, T.,Bonnal, S.,Simon, B.,Zanier, K.,Gasch, A.,Rybin, V.,Valcarcel, J.,Sattler, M.
Multi-Domain Conformational Selection Underlies Pre-Mrna Splicing Regulation by U2Af
Nature, 475:408-, 2011

PubMed Abstract: Many cellular functions involve multi-domain proteins, which are composed of structurally independent modules connected by flexible linkers. Although it is often well understood how a given domain recognizes a cognate oligonucleotide or peptide motif, the dynamic interaction of multiple domains in the recognition of these ligands remains to be characterized. Here we have studied the molecular mechanisms of the recognition of the 3'-splice-site-associated polypyrimidine tract RNA by the large subunit of the human U2 snRNP auxiliary factor (U2AF65) as a key early step in pre-mRNA splicing. We show that the tandem RNA recognition motif domains of U2AF65 adopt two remarkably distinct domain arrangements in the absence or presence of a strong (that is, high affinity) polypyrimidine tract. Recognition of sequence variations in the polypyrimidine tract RNA involves a population shift between these closed and open conformations. The equilibrium between the two conformations functions as a molecular rheostat that quantitatively correlates the natural variations in polypyrimidine tract nucleotide composition, length and functional strength to the efficiency to recruit U2 snRNP to the intron during spliceosome assembly. Mutations that shift the conformational equilibrium without directly affecting RNA binding modulate splicing activity accordingly. Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins.

PubMed: 21753750
DOI: 10.1038/NATURE10171

実験手法

SOLUTION NMR