Allosteric and transport behavior analyses of a fucose transporter with network models

Abstract

The major facilitator superfamily (MFS) is an important and widespread family of secondary membrane transporters. Recently, an outward-open structure of MFS, the fucose/H⁺ symporter FucP was determined by X-ray crystallography. In this article, the outward-open form of FucP is analyzed by elastic network models. It is found that the periplasmic half region has remarkable fluctuation, and the closure of the periplasmic half is the most dominant conformational change for outward-open conformation of FucP. To ascertain the process of transport, an adaptive anisotropic network model is applied to explore the allosteric transitions of FucP. In particular, our simulation not only yields the intermediate states similar to that seen in the EmrD crystal structure, but also exhibits the whole transport process of FucP. On the basis of the coarse-grained analyses, we propose a new working model of how FucP mediates the symport of L-fucose and a proton. The allosteric and transport knowledge of FucP revealed in this work can provide some insights into the mechanism studies of MFS and other transport proteins.