Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 116, Issue 1, Pages 245-254Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1817239116
Keywords
crystal structure; LasR; Pseudomonas aeruginosa; quorum sensing; homoserine lactone
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Funding
- Howard Hughes Medical Institute, National Institutes of Health [5R37GM065859]
- National Science Foundation [MCB-1713731]
- National Institute of General Medical Sciences [T32GM007388]
- Jane Coffin Childs Memorial Fund for Biomedical Research Postdoctoral Fellowship
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Quorum sensing is a cell-cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use the Pseudomonas aeruginosa LasR quorum-sensing receptor to explore signal discrimination. The cognate autoinducer, 30C(12) homoserine lactone (30C(12)HSL), is a more potent activator of LasR than other homoserine lactones. However, other homoserine lactones can elicit LasR-dependent quorum-sensing responses, showing that LasR displays ligand promiscuity. We identify mutants that alter which homoserine lactones LasR detects. Substitution at residue 5129 decreases the LasR response to 30C(12)H5L, while enhancing discrimination against noncognate autoinducers. Conversely, the LasR L130F mutation increases the potency of 30C(12)H5L and other homoserine lactones. We solve crystal structures of LasR ligand-binding domains complexed with noncognate autoinducers. Comparison with existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop near the ligand-binding site. We show that LasR variants with modified ligand preferences exhibit altered quorum-sensing responses to autoinducers in vivo. We suggest that possessing some ligand promiscuity endows LasR with the ability to optimally regulate quorum-sensing traits.
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