Sandbox

From Proteopedia

NolR

The symbiosis between rhizobial microbes and legume plants is fundamental to sustainable agriculture and ecological nitrogen cycling. This partnership requires coordinated expression of multiple genes to establish nitrogen-fixing nodules, with **NolR serving as a global transcriptional regulator** controlling this critical developmental process across diverse *Rhizobium* species.

We present the first high-resolution X-ray crystal structures of NolR in both unliganded and DNA-bound forms, revealing its complex interactions with asymmetric operator sequences. Analysis of NolR complexed with two different 22-base pair operator DNA sequences (oligos AT and AA) demonstrates that this **homodimeric transcription factor adopts a winged helix-turn-helix fold** and recognizes DNA through a combination of positively charged surface residues that engage the DNA phosphate backbone and specific base contacts.

The most striking finding is a **conformational switching mechanism involving Gln56**, which alters its position to accommodate variation in target DNA sequences without changing overall binding affinity. This elegant mechanism allows NolR to regulate multiple nodulation and symbiosis genes with different operator sequences through modulation of thermodynamic binding contributions. The conformational flexibility of this key residue represents a novel regulatory strategy in the ArsR/SmtB transcription factor family.

These structural studies provide unprecedented molecular insight into **how NolR functions as a global regulatory hub**, proposing two distinct regulatory models for differential gene expression during nodule formation and symbiotic nitrogen fixation. This work illuminates the structural basis for one of nature's most important agricultural and ecological partnerships.