6MVN

LasR LBD L130F:3OC10HSL complex

Summary for 6MVN

• Entry DOI: 10.2210/pdb6mvn/pdb
• Descriptor: Transcriptional regulator LasR, 3-oxo-N-[(3S)-2-oxotetrahydrofuran-3-yl]decanamide (3 entities in total)
• Functional Keywords: transcriptional activator, 3-oxo-n-[(3s)-2-oxotetrahydrofuran-3-yl]decanamide, transcription
• Biological source: Pseudomonas aeruginosa (strain UCBPP-PA14)
• Total number of polymer chains: 2
• Total formula weight: 53901.73

Authors

Bassler, B.L.,Paczkowski, J.E. (deposition date: 2018-10-26, release date: 2019-01-16, Last modification date: 2024-03-13)

Primary citation

McCready, A.R.,Paczkowski, J.E.,Henke, B.R.,Bassler, B.L.
Structural determinants driving homoserine lactone ligand selection in thePseudomonas aeruginosaLasR quorum-sensing receptor.
Proc. Natl. Acad. Sci. U.S.A., 116:245-254, 2019

PubMed Abstract: 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 LasR quorum-sensing receptor to explore signal discrimination. The cognate autoinducer, 3OC homoserine lactone (3OCHSL), 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 S129 decreases the LasR response to 3OCHSL, while enhancing discrimination against noncognate autoinducers. Conversely, the LasR L130F mutation increases the potency of 3OCHSL 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.

PubMed: 30559209
DOI: 10.1073/pnas.1817239116

Experimental method

X-RAY DIFFRACTION (2.2 Å)