Structural Model of the Bilitranslocase Transmembrane Domain Supported by NMR and FRET Data

PLoS One. 2015 Aug 20;10(8):e0135455. doi: 10.1371/journal.pone.0135455. eCollection 2015.


We present a 3D model of the four transmembrane (TM) helical regions of bilitranslocase (BTL), a structurally uncharacterized protein that transports organic anions across the cell membrane. The model was computed by considering helix-helix interactions as primary constraints, using Monte Carlo simulations. The interactions between the TM2 and TM3 segments have been confirmed by Förster resonance energy transfer (FRET) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy, increasing our confidence in the model. Several insights into the BTL transport mechanism were obtained by analyzing the model. For example, the observed cis-trans Leu-Pro peptide bond isomerization in the TM3 fragment may indicate a key conformational change during anion transport by BTL. Our structural model of BTL may facilitate further studies, including drug discovery.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Membrane / metabolism
  • Ceruloplasmin
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Membrane Proteins / chemistry*
  • Micelles
  • Models, Structural
  • Monte Carlo Method
  • Nuclear Magnetic Resonance, Biomolecular
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Membrane Proteins
  • Micelles
  • Ceruloplasmin
  • bilitranslocase