An atypical segment swap in the DN and DC domains of the Acr_tran family resistance-nodulation-cell division pump

J Struct Biol. 2016 Dec;196(3):358-363. doi: 10.1016/j.jsb.2016.08.004. Epub 2016 Aug 16.


Domain/segment swapping is an exchange of equivalent secondary structure element(s) among two or more protein domains resulting in the reconstitution of the original fold while simultaneously causing oligomerization. Here we report an example of the outer membrane factor docking region of the Acr_tran family (PF00873) resistance-nodulation-cell division pump, in which a swapped, misfolded state, of the ferredoxin-like fold of the DN and DC domains, effectuates oligomerization. The atypical segment swap and the associated displacement of a region of the ferredoxin-like fold leads to a topology that is distinct from the original fold. To our knowledge, such segment swaps and associated fold change are rare. This exemplifies the role of functional constraints including oligomerization that determine the interplay between sequence and the three-dimensional structure of proteins.

Keywords: Domain duplication; Domain swapping; Fold change; Membrane proteins; Metamorphic proteins; RND pump.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics*
  • Cell Division
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / ultrastructure
  • Models, Molecular
  • Multidrug Resistance-Associated Proteins / chemistry*
  • Multidrug Resistance-Associated Proteins / ultrastructure
  • Protein Domains
  • Protein Folding
  • Protein Multimerization / genetics
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Proteins / ultrastructure
  • Sequence Homology, Amino Acid


  • AcrB protein, E coli
  • Escherichia coli Proteins
  • Multidrug Resistance-Associated Proteins
  • Proteins