5NJ8

Structural basis for aryl hydrocarbon receptor mediated gene activation

5NJ8 の概要

• エントリーDOI: 10.2210/pdb5nj8/pdb
• 分子名称: Aryl hydrocarbon receptor, Aryl hydrocarbon receptor nuclear translocator, DNA (5'-D(*GP*GP*TP*CP*AP*CP*GP*CP*AP*AP*CP*C)-3'), ... (6 entities in total)
• 機能のキーワード: basic helix loop helix pas domain transcription factor, transcription
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 126500.73

構造登録者

Daumke, O.,Schulte, K.W. (登録日: 2017-03-28, 公開日: 2017-06-28, 最終更新日: 2024-05-08)

主引用文献

Schulte, K.W.,Green, E.,Wilz, A.,Platten, M.,Daumke, O.
Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene Activation.
Structure, 25:1025-1033.e3, 2017

PubMed Abstract: The aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) constitute a heterodimeric basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain containing transcription factor with central functions in development and cellular homeostasis. AHR is activated by xenobiotics, notably dioxin, as well as by exogenous and endogenous metabolites. Modulation of AHR activity holds promise for the treatment of diseases featuring altered cellular homeostasis, such as cancer or autoimmune disorders. Here, we present the crystal structure of a heterodimeric AHR:ARNT complex containing the PAS A and bHLH domain bound to its target DNA. The structure provides insights into the DNA binding mode of AHR and elucidates how stable dimerization of AHR:ARNT is achieved through sophisticated domain interplay via three specific interfaces. Using mutational analyses, we prove the relevance of the observed interfaces for AHR-mediated gene activation. Thus, our work establishes the structural basis of AHR assembly and DNA interaction and provides a template for targeted drug design.

PubMed: 28602820
DOI: 10.1016/j.str.2017.05.008

実験手法

X-RAY DIFFRACTION (3.3 Å)