2LXT

Allosteric communication in the KIX domain proceeds through dynamic re-packing of the hydrophobic core

2LXT の概要

• エントリーDOI: 10.2210/pdb2lxt/pdb
• 関連するPDBエントリー: 2LXS
• NMR情報: BMRB: 18695
• 分子名称: CREB-binding protein, Histone-lysine N-methyltransferase MLL, Cyclic AMP-responsive element-binding protein 1 (3 entities in total)
• 機能のキーワード: creb binding protein, mixed-lineage leukemia activation domain, phosphorylated kinase inducible domain, creb, ternary complex, transferase-protein binding complex, transferase/protein binding
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cytoplasm: Q92793; Nucleus. MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164; Nucleus: P16220
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 16359.48

構造登録者

Bruschweiler, S.,Schanda, P.,Konrat, R.,Tollinger, M. (登録日: 2012-08-31, 公開日: 2013-06-12, 最終更新日: 2024-11-20)

主引用文献

Bruschweiler, S.,Konrat, R.,Tollinger, M.
Allosteric communication in the KIX domain proceeds through dynamic repacking of the hydrophobic core.
Acs Chem.Biol., 8:1600-1610, 2013

PubMed Abstract: The KIX domain of the transcriptional coactivator CREB binding protein (CBP) co-operatively mediates interactions between transcription factors. Binding of the transcription factor mixed-lineage leukemia (MLL) induces the formation of a low-populated conformer of KIX that resembles the conformation of the KIX domain in the presence of a second transcription factor molecule. NMR spin relaxation studies have previously shown that allosteric coupling proceeds through a network of hydrophobic core residues that bridge the two binding sites. Here we describe high-resolution NMR solution structures of the binary complex of KIX with MLL and the ternary complex of KIX formed with MLL and phosphorylated kinase inducible domain of CREB (pKID) as a second ligand. We show that binding of pKID to the binary complex of KIX with MLL is accompanied by a defined repacking of the allosteric network in the hydrophobic core of the protein. Rotamer populations derived from methyl group (13)C chemical shifts reveal a dynamic contribution to the repacking process that is not captured by the structural coordinates and exemplify the dynamic nature of allosteric communication in the KIX domain.

PubMed: 23651431
DOI: 10.1021/cb4002188

実験手法

SOLUTION NMR