Identification of Ligand Specificity Determinants in Lantibiotic Bovicin HJ50 and the Receptor BovK,a Multitransmembrane Histidine Kinase |
| |
Authors: | Kunling Teng Jie Zhang Xue Zhang Xiaoxuan Ge Yong Gao Jian Wang Yuheng Lin Jin Zhong |
| |
Institution: | From the ‡State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences and ;§University of Chinese Academy of Sciences, Beijing 100101, P.R. China |
| |
Abstract: | Lantibiotic bovicin HJ50 is produced by Streptococcus bovis HJ50 and acts as the extracellular signal to autoregulate its own biosynthesis through BovK/R two-component system. Bovicin HJ50 shows a linear N-terminal and glubolar C-terminal structure, and the sensor histidine kinase BovK contains eight transmembrane segments lacking any extensive surface-exposed sensory domain. The signal recognition mechanism between bovicin HJ50 and BovK is still unknown. We performed saturated alanine scanning mutagenesis and other amino acid substitutions on bovicin HJ50 using a semi-in vitro biosynthesis. Results of the mutants inducing activities indicated that several charged and hydrophobic amino acids in ring B of bovicin HJ50, as well as two glycines were key residues to recognize BovK. Circular dichroism analyses indicated that both glycines contributed to bovicin HJ50 structural changes in the membrane. Biotin-labeled bovicin HJ50 could interact with the N-terminal sensor of BovK, and several charged residues and a conserved hydrophobic region in the N-terminal portion of BovK sensor domain were important for interacting with the signal bovicin HJ50. By combining the results, we suggested a mechanism of bovicin HJ50 recognizing and activating BovK mainly through electrostatic and hydrophobic interactions. |
| |
Keywords: | Antimicrobial Peptides Histidine Kinases Membrane Proteins Protein-Protein Interactions Signal Transduction BovK Bovicin HJ50 Lantibiotics |
|
|