Functional Annotation of Bacterial Signal Transduction Systems: Progress and Challenges

被引:19
|
作者
Martin-Mora, David [1 ]
Fernandez, Matilde [1 ]
Velando, Felix [1 ]
Ortega, Alvaro [2 ]
Gavira, Jose A. [3 ]
Matilla, Miguel A. [1 ]
Krell, Tino [1 ]
机构
[1] CSIC, Estn Expt Zaidin, Dept Environm Protect, Prof Albareda 1, E-18008 Granada, Spain
[2] Univ Murcia, Dept Biochem & Mol Biol B & Immunol, Fac Chem, Campus Espinardo,Reg Campus Int Excellence, E-30100 Murcia, Spain
[3] UGR, CSIC, IACT, Lab Estudios Cristalog, Ave Palmeras 4, Armilla 18100, Spain
关键词
bacterial signal transduction systems; chemotaxis; transcriptional regulators; chemoreceptors; sensor kinases; SINORHIZOBIUM-MELILOTI CHEMOTAXIS; PROTEIN-PROTEIN INTERACTIONS; PSEUDOMONAS-AERUGINOSA; AMINO-ACIDS; ESCHERICHIA-COLI; ENERGY TAXIS; TRANSCRIPTIONAL REGULATOR; MEDIATES CHEMOTAXIS; CRYSTAL-STRUCTURES; SENSORY PROTEINS;
D O I
10.3390/ijms19123755
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Bacteria possess a large number of signal transduction systems that sense and respond to different environmental cues. Most frequently these are transcriptional regulators, two-component systems and chemosensory pathways. A major bottleneck in the field of signal transduction is the lack of information on signal molecules that modulate the activity of the large majority of these systems. We review here the progress made in the functional annotation of sensor proteins using high-throughput ligand screening approaches of purified sensor proteins or individual ligand binding domains. In these assays, the alteration in protein thermal stability following ligand binding is monitored using Differential Scanning Fluorimetry. We illustrate on several examples how the identification of the sensor protein ligand has facilitated the elucidation of the molecular mechanism of the regulatory process. We will also discuss the use of virtual ligand screening approaches to identify sensor protein ligands. Both approaches have been successfully applied to functionally annotate a significant number of bacterial sensor proteins but can also be used to study proteins from other kingdoms. The major challenge consists in the study of sensor proteins that do not recognize signal molecules directly, but that are activated by signal molecule-loaded binding proteins.
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页数:22
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