3PMC: Crystal Structure Of The Sporulation Inhibitor Pxo2-61 From Bacillus Anthracis

Pathogenesis by Bacillus anthracis requires coordination between two distinct activities: plasmid-encoded virulence factor expression (which protects vegetative cells from immune surveillance during outgrowth and replication) and chromosomally encoded sporulation (required only during the final stages of infection). Sporulation is regulated by at least five sensor histidine kinases that are activated in response to various environmental cues. One of these kinases, BA2291, harbors a sensor domain that has approximately 35% sequence identity with two plasmid proteins, pXO1-118 and pXO2-61. Because overexpression of pXO2-61 (or pXO1-118) inhibits sporulation of B. anthracis in a BA2291-dependent manner, and pXO2-61 expression is strongly up-regulated by the major virulence gene regulator, AtxA, it was suggested that their function is to titrate out an environmental signal that would otherwise promote untimely sporulation. To explore this hypothesis, we determined crystal structures of both plasmid-encoded proteins. We found that they adopt a dimeric globin fold but, most unusually, do not bind heme. Instead, they house a hydrophobic tunnel and hydrophilic chamber that are occupied by fatty acid, which engages a conserved arginine and chloride ion via its carboxyl head group. In vivo, these domains may therefore recognize changes in fatty acid synthesis, chloride ion concentration, and/or pH. Structure-based comparisons with BA2291 suggest that it binds ligand and dimerizes in an analogous fashion, consistent with the titration hypothesis. Analysis of newly sequenced bacterial genomes points to the existence of a much broader family of non-heme, globin-based sensor domains, with related but distinct functionalities, that may have evolved from an ancestral heme-linked globin.
PDB ID: 3PMCDownload
MMDB ID: 88101
PDB Deposition Date: 2010/11/16
Updated in MMDB: 2011/05
Experimental Method:
x-ray diffraction
Resolution: 1.49  Å
Source Organism:
Similar Structures:
Biological Unit for 3PMC: dimeric; determined by author and by software (PISA)
Molecular Components in 3PMC
Label Count Molecule
Proteins (2 molecules)
Uncharacterized Protein Pxo2-61/bxb0075/gbaa_pxo2_0075(Gene symbol: pxo2_61)
Molecule annotation
Chemicals (34 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB