2K27

Solution structure of Human Pax8 Paired Box Domain

2K27 の概要

• エントリーDOI: 10.2210/pdb2k27/pdb
• NMR情報: BMRB: 15693
• 分子名称: Paired box protein Pax-8 (1 entity in total)
• 機能のキーワード: paired domain, pax8, solution structure, triple frequency, 3d nmr, induced fit, alternative splicing, developmental protein, differentiation, disease mutation, dna-binding, nucleus, paired box, phosphoprotein, polymorphism, transcription, transcription regulation, transcription regulator
• 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: 17447.94

構造登録者

Codutti, L.,Esposito, G.,Corazza, A.,Fogolari, F.,Tell, G.,Vascotto, C.,van Ingen, H.,Boelens, R.,Viglino, P.,Quadrifoglio, F. (登録日: 2008-03-26, 公開日: 2008-09-30, 最終更新日: 2024-05-08)

主引用文献

Codutti, L.,van Ingen, H.,Vascotto, C.,Fogolari, F.,Corazza, A.,Tell, G.,Quadrifoglio, F.,Viglino, P.,Boelens, R.,Esposito, G.
The Solution Structure of DNA-free Pax-8 Paired Box Domain Accounts for Redox Regulation of Transcriptional Activity in the Pax Protein Family.
J.Biol.Chem., 283:33321-33328, 2008

PubMed Abstract: Pax-8 is a transcription factor belonging to the PAX genes superfamily and its crucial role has been proven both in embryo and in the adult organism. Pax-8 activity is regulated via a redox-based mechanism centered on the glutathionylation of specific cysteines in the N-terminal region (Cys45 and Cys57). These residues belong to a highly evolutionary conserved DNA binding site: the Paired Box (Prd) domain. Crystallographic protein-DNA complexes of the homologues Pax-6 and Pax-5 showed a bipartite Prd domain consisting of two helix-turn-helix (HTH) motifs separated by an extended linker region. Here, by means of nuclear magnetic resonance, we show for the first time that the HTH motifs are largely defined in the unbound Pax-8 Prd domain. Our findings contrast with previous induced fit models, in which Pax-8 is supposed to largely fold upon DNA binding. Importantly, our data provide the structural basis for the enhanced chemical reactivity of residues Cys45 and Cys57 and explain clinical missense mutations that are not obviously related to the DNA binding interface of the paired box domain. Finally, sequence conservation suggests that our findings could be a general feature of the Pax family transcription factors.

PubMed: 18829450
DOI: 10.1074/jbc.M805717200

実験手法

SOLUTION NMR