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Research Themes Novel Proteins

Seeing HetR

SBKB [doi:10.1038/sbkb.2011.27]
Featured Article - July 2011
Short description: The structure of the transcription factor HetR now indicates how it might function during cyanobacterial differentiatation.

HetR dimer structure. The N and C termini are indicated. The DNA binding region is green, the hood domains blue and the flap domains are shown in magenta.

Some cyanobacteria, including Anabaena, which grows as a filament, can carry out both photosynthesis and nitrogen fixation. To conduct these processes efficiently, specialized cells called heterocysts that are regularly spaced in a filament conduct nitrogen fixation, but not photosynthesis. These cells are morphologically distinct, and their regular spacing is mediated through a gradient-signaling system ensuring that a new heterocyst will develop centrally along the filament between two others. This system is now known to depend on a peptide, PatS, that inhibits HetR, a factor implicated early on in studies of this patterning system by genetic analysis.

Joachimiak (PSI MCSG), Haselkorn and colleagues have now solved the crystal structure of HetR. To facilitate this goal, and overcome the difficulty of obtaining Anabaena HetR crystals, the authors first examined HetR orthologs from different species and focused on Fischerella, which grows at higher temperatures, as a likely candidate for obtaining crystals. The authors showed that Fischerella HetR complements Anabaena HetR mutants and solved the structure. The structure is unusual, with the N-terminal and C-terminal domains, called the flap and hood domains, respectively, forming open conformations. These regions are closely involved in forming a dimer. HetR had been suggested to exist as a dimer, but an examination of the positions of cysteine residues in the structure argues that this does not involve a disulfide bridge, as suggested previously.

The central domain is the one that most closely resembles known structural motifs, and consists of a helix-turn-helix, which is likely to be the DNA-binding domain. Through mutagenesis it was shown that residues in this region are needed for binding to an oligonucleotide containing the HetR recognition sequence. In addition, mutagenesis of residues implicated in DNA binding does not complement the HetR mutant. The authors argue that this region can probably accommodate DNA 16 bp to 17 bp long, though engagement of other domains could extend this length.

As HetR is regulated by a peptide, either PatS or a peptide derived from it, the authors analyzed the structure for possible binding regions. Possible regions were identified, some of which might interfere with DNA binding, thus providing a rationale for inhibition. Further testing will examine the mechanism by which the regions in this unusual structure act together to promote precise spatial differentiation.

Sabbi Lall


  1. Y. Kim et al. Structure of transcription factor HetR required for heterocyst differentiation in cyanobacteria.
    Proc. Natl. Acad. Sci. USA (31 May 2011). doi:10.1073/pnas.1106840108

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