E. coli trp Repressor Forms a Domain-Swapped Array in Aqueous Alcohol

Catherine L Lawson, Brian Benoff, Tatyana Berger, Helen M Berman, Jannette Carey
2004 Structure  
fold (Figure 1A), the trpR dimer itself has been consid-Department of Chemistry and Chemical Biology ered a probable example of quasi-domain swapping 610 Taylor Road (Hakansson and Linse, 2002; Schlunegger et al., 1997). Piscataway, New Jersey 08854 An apparent monomeric homolog of trpR has recently 2 Princeton University been identified (Erzberger et al., 2002). To our knowl-Department of Chemistry edge, the structure we present here is the first example Princeton, New Jersey 08544 of an
more » ... d, extended 3D network formed by domain swapping. The smallest functional unit of trpR is the dimer (Joa-Summary chimiak et al., 1983a), but higher order association is well documented. When bound to tandem DNA sites, The E. coli trp repressor (trpR) homodimer recognizes trpR dimers associate in a 2-fold symmetric manner its palindromic DNA binding site through a pair of flexithrough a limited, predominantly hydrophobic interacble helix-turn-helix (HTH) motifs displayed on an intertion between flexible N-terminal arms and a concave twined helical core. Flexible N-terminal arms mediate surface adjacent to and involving the HTH (Figure 1B) association between dimers bound to tandem DNA (Lawson and Carey, 1993). TrpR dimers also associate sites. The 2.5 A ˚X-ray structure of trpR crystallized in in the absence of DNA, yielding predominantly tetramers 30% (v/v) isopropanol reveals a substantial conformabut also higher order species (Fernando and Royer, tional rearrangement of HTH motifs and N-terminal 1992; Martin et al., 1994). Biochemical, mutational, and arms, with the protein appearing in the unusual form structural evidence support the hypothesis first put forof an ordered 3D domain-swapped supramolecular ward by Royer that dimer-dimer interactions in the abarray. Small angle X-ray scattering measurements sence of DNA involve N-terminal arm contacts similar show that the self-association properties of trpR in to those made on DNA (Chae et al., 1999; Mackintosh solution are fundamentally altered by isopropanol.
doi:10.1016/j.str.2004.03.019 pmid:15274929 pmcid:PMC3228604 fatcat:6dnpgbqtrbc25mtjllhwthyj2m