N15 Cro and λ Cro: Orthologous DNA-binding domains with completely different but equally effective homodimer interfaces

Matthew S. Dubrava, Wendy M. Ingram, Sue A. Roberts, Andrzej Weichsel, William R. Montfort, Matthew H.J. Cordes

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Bacteriophage Cro proteins bind to target DNA as dimers but do not all dimerize with equal strength, and differ in fold in the region of the dimer interface. We report the structure of the Cro protein from Enterobacteria phage N15 at 1.05 Å resolution. The subunit fold contains five a-helices and is closely similar to the structure of P22 Cro (1.3 Å backbone room mean square difference over 52 residues), but quite different from that of λ Cro, a structurally diverged member of this family with a mixed α-helix/β-sheet fold. N15 Cro crystallizes as a biological dimer with an extensive interface (1303 Å2 change in accessible surface area per dimer) and also dimerizes in solution with a Kd of 5.1 ± 1.5 mM. Its dimerization is much stronger than that of its structural homolog P22 Cro, which does not self-associate detectably in solution. Instead, the level of self-association and interfacial area for N15 Cro is similar to that of λ Cro, even though these two orthologs do not share the same fold and have dimer interfaces that are qualitatively different in structure. The common Cro ancestor is thought to be an all-helical monomer similar to P22 Cro. We propose that two Cro descendants independently developed stronger dimerization by entirely different mechanisms. Published by Cold Spring Harbor Laboratory Press.

Original languageEnglish (US)
Pages (from-to)803-812
Number of pages10
JournalProtein Science
Volume17
Issue number5
DOIs
StatePublished - May 1 2008

Keywords

  • Evolution of oligomerization
  • Helix-turn-helix
  • Structural evolution
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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