Solution structure of switch Arc, a mutant with 310 helices replacing a wild-type β-ribbon

Matthew H.J. Cordes, Nathan P. Walsh, C. James McKnight, Robert T. Sauer

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Adjacent N11L and L12N mutations in the antiparallel β-ribbon of Arc repressor result in dramatic changes in local structure in which each β-strand is replaced by a right-handed helix. The full solution structure of this "switch" Arc mutant shows that irregular 310 helices compose the new secondary structure. This structural metamorphosis conserves the number of main-chain and side-chain to main-chain hydrogen bonds and the number of fully buried core residues. Apart from a slight widening of the interhelical angle between α-helices A and B and changes in side-chain conformation of a few core residues in Arc, no large-scale structural adjustments in the remainder of the protein are necessary to accommodate the ribbon-to-helix change. Nevertheless, some changes in hydrogen-exchange rates are observed, even in regions that have very similar structures in the two proteins. The surface of switch Arc is packed poorly compared to wild-type, leading to ∼1000Å2 of additional solvent-accessible surface area, and the N termini of the 310 helices make unfavorable head-to-head electrostatic interactions. These structural features account for the positive m value and salt dependence of the ribbon-to-helix transition in Arc-N11L, a variant that can adopt either the mutant or wild-type structures. The tertiary fold is capped in different ways in switch and wild-type Arc, showing how stepwise evolutionary transformations can arise through small changes in amino acid sequence.

Original languageEnglish (US)
Pages (from-to)899-909
Number of pages11
JournalJournal of Molecular Biology
Issue number3
StatePublished - Feb 21 2003


  • Binary pattern
  • Core packing
  • NMR structure
  • Protein evolution
  • Protein folding

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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