4G3W

Crystal structure of a. aeolicus nlh1 gaf domain in an inactive state

4G3W の概要

• エントリーDOI: 10.2210/pdb4g3w/pdb
• 関連するPDBエントリー: 4G3K 4G3V
• 分子名称: Transcriptional regulator nlh1 (2 entities in total)
• 機能のキーワード: gaf domain, transcription regulator
• 由来する生物種: Aquifex aeolicus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 19339.67

構造登録者

Batchelor, J.D.,Wang, A.,Lee, P.,Doucleff, M.,Wemmer, D.E. (登録日: 2012-07-15, 公開日: 2013-05-29, 最終更新日: 2024-02-28)

主引用文献

Batchelor, J.D.,Lee, P.S.,Wang, A.C.,Doucleff, M.,Wemmer, D.E.
Structural mechanism of GAF-regulated delta(54) activators from Aquifex aeolicus
J.Mol.Biol., 425:156-170, 2013

PubMed Abstract: The σ subunits of bacterial RNA polymerase occur in many variant forms and confer promoter specificity to the holopolymerase. Members of the σ(54) family of σ subunits require the action of a 'transcriptional activator' protein to open the promoter and initiate transcription. The activator proteins undergo regulated assembly from inactive dimers to hexamers that are active ATPases. These contact σ(54) directly and, through ATP hydrolysis, drive a conformational change that enables promoter opening. σ(54) activators use several different kinds of regulatory domains to respond to a wide variety of intracellular signals. One common regulatory module, the GAF domain, is used by σ(54) activators to sense small-molecule ligands. The structural basis for GAF domain regulation in σ(54) activators has not previously been reported. Here, we present crystal structures of GAF regulatory domains for Aquifex aeolicus σ(54) activators NifA-like homolog (Nlh)2 and Nlh1 in three functional states-an 'open', ATPase-inactive state; a 'closed', ATPase-inactive state; and a 'closed', ligand-bound, ATPase-active state. We also present small-angle X-ray scattering data for Nlh2-linked GAF-ATPase domains in the inactive state. These GAF domain dimers regulate σ(54) activator proteins by holding the ATPase domains in an inactive dimer conformation. Ligand binding of Nlh1 dramatically remodels the GAF domain dimer interface, disrupting the contacts with the ATPase domains. This mechanism has strong parallels to the response to phosphorylation in some two-component regulated σ(54) activators. We describe a structural mechanism of GAF-mediated enzyme regulation that appears to be conserved among humans, plants, and bacteria.

PubMed: 23123379
DOI: 10.1016/j.jmb.2012.10.017

実験手法

X-RAY DIFFRACTION (2.7 Å)