Attractant and repellent induce opposing changes in the four-helix bundle ligand-binding domain of a bacterial chemoreceptor

• Published in: PLoS biology 2023-12, Vol.21 (12), p.e3002429-e3002429
• Main Authors: Guo, Lu, Wang, Yun-Hao, Cui, Rui, Huang, Zhou, Hong, Yuan, Qian, Jia-Wei, Ni, Bin, Xu, An-Ming, Jiang, Cheng-Ying, Zhulin, Igor B, Liu, Shuang-Jiang, Li, De-Feng
• Format: Article
• Language: English
• Subjects: Amino acid substitution; Amino acids; Attractants; Bacteria; Binding sites; Biofilms; Biology and Life Sciences; Chemoreceptors; Chemotaxis; E coli; Identification and classification; Kinases; Ligands; Malate; Medicine and Health Sciences; Oligomerization; Physical Sciences; Properties; Proteins; Repellents; Research and Analysis Methods; Short Reports
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3002429

Motile bacteria navigate toward favorable conditions and away from unfavorable environments using chemotaxis. Mechanisms of sensing attractants are well understood; however, molecular aspects of how bacteria sense repellents have not been established. Here, we identified malate as a repellent recognized by the MCP2201 chemoreceptor in a bacterium Comamonas testosteroni and showed that it binds to the same site as an attractant citrate. Binding determinants for a repellent and an attractant had only minor differences, and a single amino acid substitution in the binding site inverted the response to malate from a repellent to an attractant. We found that malate and citrate affect the oligomerization state of the ligand-binding domain in opposing way. We also observed opposing effects of repellent and attractant binding on the orientation of an alpha helix connecting the sensory domain to the transmembrane helix. We propose a model to illustrate how positive and negative signals might be generated.