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

European Biophysics Journal : EBJ
Gunnar Jeschke

Abstract

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.

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Citations

May 15, 2013·Structure·Paul J FockeH Peter Larsson
Mar 20, 2013·Molecular Aspects of Medicine·Dimitrios FotiadisManuel Palacín
Feb 14, 2018·Microbiology and Molecular Biology Reviews : MMBR·Weiping ZhangJian Chen
Oct 1, 2014·Molecular and Cellular Biology·Kassem GhaddarBruno André
Jan 23, 2014·The Journal of Biological Chemistry·Kassem GhaddarMartine Prévost
Jan 6, 2016·The Journal of Biological Chemistry·Susanne BracherHeinrich Jung
Jul 17, 2021·SLAS Discovery·Mariafrancesca ScaliseCesare Indiveri

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Methods Mentioned

BETA
as
fluorescence resonance
electron paramagnetic resonance
FRET
NMR

Software Mentioned

ANM
Matlab
MMM
Updelta
ENM

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