6LKI
Two-component system protein mediate signal transduction
Summary for 6LKI
| Entry DOI | 10.2210/pdb6lki/pdb |
| Descriptor | ABC transporter, solute-binding protein, Sensor protein kinase HptS, MALONIC ACID, ... (4 entities in total) |
| Functional Keywords | two-component system, g6p sensor, signal transduction, signaling protein, signaling protein-transferase complex, signaling protein/transferase |
| Biological source | Staphylococcus aureus More |
| Total number of polymer chains | 2 |
| Total formula weight | 54447.45 |
| Authors | |
| Primary citation | 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 Cited by 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: 33199635DOI: 10.1073/pnas.1912080117 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.781 Å) |
Structure validation
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