3MPL

Crystal Structure of Bordetella pertussis BvgS VFT2 domain (Double Mutant F375E/Q461E)

3MPL の概要

• エントリーDOI: 10.2210/pdb3mpl/pdb
• 関連するPDBエントリー: 3MPK
• 分子名称: Virulence sensor protein bvgS, 1,2-ETHANEDIOL (3 entities in total)
• 機能のキーワード: venus flytrap, sensor domain, signaling protein
• 由来する生物種: Bordetella pertussis
• 細胞内の位置: Cell inner membrane; Multi-pass membrane protein (Probable): P16575
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 29661.49

構造登録者

Herrou, J.,Bompard, C.,Wintjens, R.,Dupre, E.,Willery, E.,Villeret, V.,Locht, C.,Antoine, R.,Jacob-Dubuisson, F. (登録日: 2010-04-27, 公開日: 2010-10-06, 最終更新日: 2023-09-06)

主引用文献

Herrou, J.,Bompard, C.,Wintjens, R.,Dupre, E.,Willery, E.,Villeret, V.,Locht, C.,Antoine, R.,Jacob-Dubuisson, F.
Periplasmic domain of the sensor-kinase BvgS reveals a new paradigm for the Venus flytrap mechanism.
Proc.Natl.Acad.Sci.USA, 107:17351-17355, 2010

PubMed Abstract: Two-component sensory transduction systems control important bacterial programs. In Bordetella pertussis, expression of the virulence regulon is controlled by the unorthodox BvgAS two-component system. BvgS is the prototype of a family of sensor-kinases that harbor periplasmic domains homologous to bacterial solute-binding proteins. Although BvgAS is active under laboratory conditions, no activating signal has been identified, only negative modulators. Here we show that the second periplasmic domain of BvgS interacts with modulators and adopts a Venus flytrap (VFT) fold. X-ray crystallography reveals that the two lobes of VFT2 delimitate a ligand-binding cavity enclosing fortuitous ligands. Most substitutions of putative ligand-binding residues in the VFT2 cavity keep BvgS active, and alteration of the cavity's electrostatic potential affects responsiveness to modulation. The crystal structure of this VFT2 variant conferring constitutive kinase activity to BvgS shows a closed cavity with another nonspecific ligand. Thus, VFT2 is closed and active without a specific agonist ligand, in contrast to typical VFTs. Modulators are antagonists of VFT2 that interrupt signaling. BvgAS is active for most of the B. pertussis infectious cycle, consistent with the proposed mechanism.

PubMed: 20855615
DOI: 10.1073/pnas.1006267107

実験手法

X-RAY DIFFRACTION (2.1 Å)