View source for NolR

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<span style="font-size:160%"><b>Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR (BI3323-Aug2025)</b></span>
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Paul C. Rosen, Samantha M. Horwitz, Daniel J. Brooks, Erica Kim, Joseph A. Ambarian, Lidia Waidmann, Katherine M. Davis and Gary Yellen

PNAS,  March 6, 2025, Vol. 122  No. 10 e2426324122, [https://doi.org/10.1073/pnas.2426324122] 
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==Structure Tour==

<StructureSection load='4omz' size='350' side='right' caption='Crystal Structure of NolR from Sinorhizobium fredii complex with phosphate (PDB entry [[4omz]])' scene=''>
===Abstract===
The symbiosis between rhizobial bacteria and leguminous plants is a critical ecological process leading to nitrogen fixation. This process is tightly regulated by a series of ''nod'' genes. '''NolR''' is a global regulatory protein (transcription factor) conserved across ''Sinorhizobium'' and ''Rhizobium'' species that represses these nodulation genes to optimize symbiosis. This paper presents the crystal structures of NolR in both unliganded and DNA-bound forms, revealing an asymmetric binding mechanism and a specific conformational switch that allows the protein to recognize variable DNA sequences.

===Overall Structure of NolR===
NolR is a member of the '''ArsR/SmtB family''' of transcription factors. The crystal structure reveals that the protein functions as a homodimer. Each monomer folds into a winged helix-turn-helix motif.

 Click on "<scene name='85/857155/Chain_a/2'>Chain A</scene>" of "NolR".

 Click on "<scene name='85/857155/Chain_b/2'>Chain B</scene>" of "NolR".

* '''Dimerization:''' Two alpha-helices (<scene name='85/857155/Alpha_1_and_alpha_5/1'>alpha-1 and alpha-5)</scene> from each monomer form a coiled-coil dimerization interface.
* '''DNA Binding Domain:''' A triangular set of helices (<scene name='85/857155/Alpha_2_and_alpha_4/1'>alpha-2 and alpha-4</scene>) positions the recognition helix (<scene name='85/857155/Alpha3_alpha4/1'>alpha-3 and alpha-4</scene>) for interaction with the DNA major groove.
* '''The Wing:''' A two-stranded antiparallel beta-sheet extends outward to interact with the minor groove.

===DNA Binding and Recognition===
The co-crystal structure of NolR with a 22-base pair operator sequence (<scene name='85/857155/Dna/1'>Oligo AT</scene>) reveals how the repressor recognizes its target. The NolR dimer binds to an asymmetric operator site.

Select <scene name='85/857155/Dna_binding/1'>DNA binding</scene> to visualize the binding of NolR on oligo AT rich DNA.

* '''Major Groove:''' The alpha-4 helix of each monomer inserts deep into the major groove of the DNA.
* '''Minor Groove:''' The beta-wing residues contact the minor groove.
* '''Electrostatics:''' The DNA-binding surface of NolR is positively charged, facilitating interaction with the phosphate backbone, while the opposite face is negatively charged.
* '''DNA Bending:''' Upon binding, the DNA duplex bends approximately 16.8 degrees from an ideal B-form.

===The Gln56 Conformational Switch===
A key finding of this study is the mechanism by which NolR binds to diverse operator sequences that vary at specific positions (A vs T). The authors crystallized NolR with two different DNA sequences: "Oligo AT" (consensus) and "Oligo AA" (variable).

Click <scene name='85/857155/Gln56_switch/1'>Gln56 switch</scene> to visualize the Gln56 residues that are essential for the variable binding of NolR.

* '''Consensus Binding (Oligo AT):''' In the first half-site, '''Gln56''' hydrogen bonds with Adenine 2. However, in the second half-site, the Gln56 side chain flips away from Thymine 7'.
* '''Variable Binding (Oligo AA):''' When bound to the Oligo AA sequence (where T7' is replaced by A7'), '''Gln56''' undergoes a conformational switch. It rotates to form a hydrogen bond with the new Adenine base.

===3D structures of NolR===

Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}

[[4omz]] – SfNolR – ''Sinorhibozium fredii''<br />
[[4omy]], [[4on0]] – SfNolR + DNA

===References===
* Lee SG, Krishnan HB, Jez JM. Structural basis for regulation of rhizobial nodulation and symbiosis gene expression by the regulatory protein NolR. ''Proc Natl Acad Sci U S A.'' 2014 Apr 29;111(17):6509-14. doi: 10.1073/pnas.1402243111.

===About this Page===
<!-- This section ensures you get credit -->
This page was created by '''[[User:Your_Username|Balagopal Nithin]]'''.<br>
University/Institution Name (Indian Institute of Science Education and Research,Pune)


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