Abstract
Quorum sensing (QS) enables common gram-negative bacteria to coordinate collective behaviors through small molecule signals, yet how these signals tune receptor activity remains incompletely understood. Here, we define a mechanism by which ligand structure controls function in a LuxR-type QS receptor. Using structural and biochemical analyses, we investigate MrtR from
Mesorhizobium tianshanense
and show that ligand acyl-chain length governs receptor assembly and activity. We present full-length structures of MrtR bound to activating and inhibitory ligands, revealing a switch in oligomeric state. Long-chain (C14)
N
-acyl
l
-homoserine lactones (AHLs) act as agonists by promoting intra- and intersubunit interactions that lead to homodimerization and DNA binding. In contrast, shorter (C8) AHLs fail to promote these contacts, favoring a monomeric, inactive state. Ligands of intermediate length produce graded responses consistent with partial dimer stabilization. Biochemical measurements of DNA binding, thermostability, and oligomerization, together with targeted mutagenesis, support this model and establish the functional importance of key structural contacts. These findings provide a side-by-side structural comparison of a full-length LuxR-type receptor bound to both agonist and antagonist. Our results expand the known structural and mechanistic diversity of the LuxR family and suggest mechanistic similarities between structurally distinct receptors.