6LKG

two-component system protein mediate signal transduction

6LKG の概要

• エントリーDOI: 10.2210/pdb6lkg/pdb
• 分子名称: Sensor protein kinase HptS, ABC transporter, solute-binding protein, 6-O-phosphono-alpha-D-glucopyranose, ... (4 entities in total)
• 機能のキーワード: two-component system, g6p sensor, signal transduction, signaling protein, transferase-signaling protein complex, transferase/signaling protein
• 由来する生物種: Staphylococcus aureus (strain NCTC 8325); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 109040.78

構造登録者

Wang, M.,Tao, Y. (登録日: 2019-12-19, 公開日: 2020-12-02, 最終更新日: 2024-03-27)

主引用文献

Wang, M.,Guo, Q.,Zhu, K.,Fang, B.,Yang, Y.,Teng, M.,Li, X.,Tao, Y.
Interface switch mediates signal transmission in a two-component system.
Proc.Natl.Acad.Sci.USA, 117:30433-30440, 2020

PubMed Abstract: Two-component systems (TCS), which typically consist of a membrane-embedded histidine kinase and a cytoplasmic response regulator, are the dominant signaling proteins for transduction of environmental stimuli into cellular response pathways in prokaryotic cells. HptRSA is a recently identified TCS consisting of the G6P-associated sensor protein (HptA), transmembrane histidine kinase (HptS), and cytoplasmic effector (HptR). HptRSA mediates glucose-6-phosphate (G6P) uptake to support growth and multiplication within various host cells. How the mechanism by which HptRSA perceives G6P and triggers a downstream response has remained elusive. Here, we solved the HptA structures in apo and G6P-bound states. G6P binding in the cleft between two HptA domains caused a conformational closing movement. The solved structures of HptA in complex with the periplasmic domain of HptS showed that HptA interacts with HptS through both constitutive and switchable interfaces. The G6P-free form of HptA binds to the membrane-distal side of the HptS periplasmic domain (HptSp), resulting in a parallel conformation of the HptSp protomer pair. However, once HptA associates with G6P, its intramolecular domain closure switches the HptA-HptSp contact region into the membrane-proximal domain, which causes rotation and closure of the C termini of each HptSp protomer. Through biochemical and growth assays of HptA and HptS mutant variants, we proposed a distinct mechanism of interface switch-mediated signaling transduction. Our results provide mechanistic insights into bacterial nutrient sensing and expand our understanding of the activation modes by which TCS communicates external signals.

PubMed: 33199635
DOI: 10.1073/pnas.1912080117

実験手法

X-RAY DIFFRACTION (1.948 Å)