title: Percolation of the phd repressor-operator interface.
abstract: Transcription of the P1 plasmid addiction operon, a prototypical toxin-antitoxin system, is negatively autoregulated by the products of the operon. The Phd repressor-antitoxin protein binds to 8-bp palindromic Phd-binding sites in the promoter region and thereby represses transcription. The toxin, Doc, mediates cooperative interactions between adjacent Phd-binding sites and thereby enhances repression. Here, we describe a homologous operon from Salmonella enterica serovar Typhimurium which has the same pattern of regulation but an altered repressor-operator specificity. This difference in specificity maps to the seventh amino acid of the repressor and to the symmetric first and eighth positions of the corresponding palindromic repressor-binding sites. Thus, the repressor-operator interface has coevolved so as to retain the interaction while altering the specificity. Within an alignment of homologous repressors, the seventh amino acid of the repressor is highly variable, indicating that evolutionary changes in repressor specificity may be common in this protein family. We suggest that the robust properties of the negative feedback loop, the fuzzy recognition in the operator-repressor interface, and the duplication and divergence of the repressor-binding sites have facilitated the speciation of this repressor-operator interface. These three features may allow the repressor-operator system to percolate within a nearly neutral network of single-step mutations without the necessity of invoking simultaneous mutations, low-fitness intermediates, or other improbable or rate-limiting mechanisms.
authors.affiliation: Department of Biological Sciences, University of Alabama, Huntsville, AL 35758, USA.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhao
authors.forename: Roy David
authors.initials: RD
authors.lastname: Magnuson
mesh_terms: D000595:Amino Acid Sequence; D000992:Antitoxins / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D006706:Homeostasis / Q000235:genetics; D008969:Molecular Sequence Data; D009876:Operon / Q000235:genetics*; D010957:Plasmids / Q000235:genetics; D017433:Protein Structure, Secondary; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics*; D012485:Salmonella typhi / Q000235:genetics*
chemical_list: D000992:Antitoxins; D012097:Repressor Proteins
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