A comparative study of structures and structural transitions of secondary transporters with the LeuT fold

Eur Biophys J. 2013 Mar;42(2-3):181-97. doi: 10.1007/s00249-012-0802-z. Epub 2012 May 3.


Secondary active transporters from several protein families share a core of two five-helix inverted repeats that has become known as the LeuT fold. The known high-resolution protein structures with this fold were analyzed by structural superposition of the core transmembrane domains (TMDs). Three angle parameters derived from the mean TMD axes correlate with accessibility of the central binding site from the outside or inside. Structural transitions between distinct conformations were analyzed for four proteins in terms of changes in relative TMD arrangement and in internal conformation of TMDs. Collectively moving groups of TMDs were found to be correlated in the covariance matrix of elastic network models. The main features of the structural transitions can be reproduced with the 5 % slowest normal modes of anisotropic elastic network models. These results support the rocking bundle model for the major conformational change between the outward- and inward-facing states of the protein and point to an important role for the independently moving last TMDs of each repeat in occluding access to the central binding site. Occlusion is also supported by flexing of some individual TMDs in the collectively moving bundle and hash motifs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biological Transport
  • Cell Membrane / metabolism
  • Computational Biology*
  • Crystallography, X-Ray
  • Humans
  • Membrane Transport Proteins / chemistry*
  • Membrane Transport Proteins / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • Membrane Transport Proteins