How does water pass through a sugar transporter

摘要: Certain membrane symporters, such as the sodium-glucose transporter (SGLT), have long been known to transport water along with their substrates. Although the main job of SGLT is uptake sugar molecules by utilizing Na+ gradient as energy source, experiments on oocytes revealed substantial fluxes into cell when SGLTs are transporting and (1). Thermodynamically, this not surprising. The was originally in osmotic equilibrium its surrounding, equal osmolarities (roughly determined total solute concentration) intra- extracellular solutions. increases intracellular osmolarity, thus enters until reaching a new equilibrium. Under experimental conditions, it estimated that for each molecule taken cell, ∼175 (1) must be added restore original concentration. How these pass through transporter, however, less obvious. Two complementary mechanisms (Fig. 1) proposed transport. In coupled (active) mechanism (Fig. 1 A), some take free ride enter same trip solutes passive permeation B), contrast, gives rise an accumulation near side membrane, which turn induces flux response local (2). Whereas readily explains rapid establishment immediately after started, supported fact does vanish sudden stop inhibitors. two no means mutually exclusive; fact, they could both at work contribute flux. Indeed, although significance has under debate over decade, widely agreed least portion observed arises from permeation. Recently, independent molecular dynamics (MD) studies (3,4) behaviors bacterial homolog multi-microsecond timescale, thanks power Anton, fastest computer world (created D. E. Shaw Research, New York, NY) MD simulations, provided valuable insight transporter. Figure 1 Two SGLT. For simplicity, only one shown here, whereas reality types (sugar Na+) involved. (A) A hypothetical Each step ... Both focused inward-facing structure (5), internal cavity appears closed solution. During simulations (3,4), continuous chains H-bonded protein interior frequently formed, transiently connecting bulk sides. conformation bottleneck aqueous pathway located, surprisingly, entrance. Consequently, motions residues (especially bulky chains) region play major role forming breaking of the chains, many transitions between conducting nonconducting states (3,4). Interestingly, sugar-binding site also path Nonetheless, constriction times allow pass, still too narrow sugar. were spontaneously released solution during calculated permeability similar orders magnitude aquaporins, indicating can conduct (albeit selectively) fast those dedicated channels. It noteworthy motion found significantly correlated movement. light better statistics obtained directional concomitant single sugar-release event previous simulation (6) coincidence rather than norm. Despite atomic pictures complete understanding conduction transporters requires continued efforts the theoretical fronts. Experimentally, most measurements so far performed oocytes. ideal study transport, involve factors (such presence other channels) may complicate interpretation observations. If reconstituted simpler systems liposomes or planar lipid bilayers, measurement shed light. Computationally, correlation movements closely examined worthwhile look coupling ions water. After all, current directly detected experiments. Furthermore, hydration state ion affinity pores related (7) important stability conformations (8–10). But importantly, final definitive conclusion controversy cotransport will probably come sight cycle fully elucidated details. Mapping conformational currently challenging task complex proteins transporters. Notably, research groups (11–13) made promising recent progress aspect.