Uracil/H+ symport by the FurE transporter challenges the rocking-bundle mechanism of transport in APC transporters
Additional information
Authors
Zantza I.,
Papadaki G. F.,
Raniolo S.,
Pyrris Y.,
Lambrinidis G.,
Limongelli V.,
Diallinas G.,
Mikros E.
Type
Preprint
Year
2022
Language
English
Abstract
Transporters mediate the uptake of solutes, metabolites and drugs across the cell membrane. The eukaryotic FurE nucleobase/H+ symporter of Aspergillus nidulans has been used as a model protein to address structure-function relationships in the APC transporter superfamily, members of which are characterized by the LeuT-fold and seem to operate by the so-called ‘rocking-bundle’ mechanism. In this study, we reveal the binding mode, translocation and release pathway of uracil/H+ by FurE, using path collective variable, funnel metadynamics and rationally designed mutational analysis. Our study reveals a step-wise, induced-fit, mechanism of ordered sequential transport of proton and uracil, which in turn suggests that the FurE symporter, and probably structurally similar transporters, functions as a multi-step gated pore, rather than employing ‘rocking’ of compact domains, as generally proposed for APC transporters. In addition, our work further supports the emerging concept that specific elements of cytosolic terminal regions of transporters might be functionally important.
Keywords
Aspergillus nidulans, NCS1, Fungal, Specificity, Structure-function
Periodico
Journal of molecular biology
Volume
435
Number ( Month )
19
Diffusion
License
Rights reserved
Visibility
Public
Status open access
Green
