Structural Biology of the Major Facilitator Superfamily Transporters

Abstract

The ancient and ubiquitous major facilitator superfamily (MFS) represents the largest secondary transporter family and plays a crucial role in a multitude of physiological processes. MFS proteins transport a broad spectrum of ions and solutes across membranes via facilitated diffusion, symport, or antiport. In recent years, remarkable advances in understanding the structural biology of the MFS transporters have been made. This article reviews the history, classification, and general features of the MFS proteins; summarizes recent structural progress with a focus on the sugar porter family transporters exemplified by GLUT1; and discusses the molecular mechanisms of substrate binding, alternating access, and cotransport coupling.

Local Anesthetics and Antipsychotic Phenothiazines Interact Nonspecifically with Membranes and Inhibit Hexose Transporters in Yeast

“…We acknowledge that the aforementioned model alone cannot explain the specificity of Hxts because the mechanism is applicable to other transporters/channels that severely change the structures on membranes (Yan 2015). Thus, another model is also required ( Figure 8B).…”

NRT1.5/NPF7.3 Functions as a Proton-Coupled H+/K+ Antiporter for K+ Loading into the Xylem in Arabidopsis

“…The substrate specificity of NRT1/PTR transporters is mainly determined by the specific side chains that line the aqueous pocket at the center of the membrane (Parker and Newstead, 2014;Sun et al, 2014;Yan, 2015). However, how plant NRT1/PTR transporters are able to recognize and transport diverse substrates remains unknown.…”

“…In plants, NO 3 2 absorption and transport are mainly conducted by the nitrate transporters from two families NRT1/PTR (Nitrate Transporter 1/ Peptide Transporter) and NRT2. Both families belong to the major facilitator superfamily that represents the largest secondary active transporters in all species (Pao et al, 1998;Law et al, 2008;Yan, 2015). The NRT1/PTR family is also known as the POT (protondependent oligopeptide transporter) family, which is present in all living organisms and prevalent in higher plants, referred to as the NPF (NRT1/PTR family) (Steiner et al, 1995;Daniel et al, 2006;Léran et al, 2014).…”

Using cellular fitness to map the structure and function of a major facilitator superfamily effluxer

“…In addition to TetB, there are many other MFS transporters, which contribute to single and multidrug resistance in a wide variety of pathogens and their thorough characterization is of great interest (Fluman & Bibi, 2009; Alegre et al , 2016). Despite the low percentage of protein sequence similarity among MFS transporters, their overall structure is largely conserved with a general understanding of how specific regions of the transporter contribute to substrate binding and/or pumping efficiency (Yan, 2015; Quistgaard et al , 2016). …”