Binding affinity of lactose permease is not altered by the H
            <sup>+</sup>
            electrochemical gradient

Guan, Lan; Kaback, H. Ronald

doi:10.1073/pnas.0404936101

Cited by 62 publications

(61 citation statements)

References 42 publications

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“…electrochemical H ϩ gradient, indicated that the H ϩ effect is not related to changes in the transporter affinity for the substrate (24). Thus, our present data cannot be interpreted as indicating the occurrence of Na ϩ -driven changes in the substrate binding site(s) leading to increased affinity for ascorbic acid, as opposed to conformational changes that directly affect the substrate translocation steps (see Fig.…”

Section: Melanoma Cells Express a Single Ascorbic Acid Transportermentioning

confidence: 62%

Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2

Godoy

Ormazábal

Moraga-Cid

et al. 2007

Journal of Biological Chemistry

102

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Section: Melanoma Cells Express a Single Ascorbic Acid Transportermentioning

confidence: 62%

Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2

Godoy

Ormazábal

Moraga-Cid

et al. 2007

Journal of Biological Chemistry

102

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“…The differences in sugar affinity and selectivity for cotranport in the two directions under the same driving forces suggest differences in the architecture of the outward-and inwardfacing sugar binding sites. This is different from lac permease where it appears that there is one lactose-binding site that is alternatively exposed to the two sides of the plasma membrane (Abramson et al, 2003;Guan & Kaback, 2004).…”

Section: Discussionmentioning

confidence: 75%

Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter

2005

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This study investigates the reverse mode of the Na + /glucose cotransporter (SGLT1). In giant excised inside-out membrane patches from Xenopus laevis oocytes expressing rabbit SGLT1, application of α-methyl-D-glucopyranoside (αMDG) to the cytoplasmic solution induced an outward current from cytosolic to external membrane surface. The outward current was Na + -and sugar-dependent, and was blocked by phlorizin, a specific inhibitor of SGLT1. The currentvoltage relationship saturated at positive membrane voltages (30-50 mV), and approached zero at − 150 mV. The half-maximal concentration for αMDG-evoked outward current ( ) was 35 mM (at 0 mV). In comparison, for forward sugar transport was 0.15 mM (at 0 mV). was similar for forward and reverse transport (≈35 mM at 0 mV). Specificity of SGLT1 for reverse transport was: αMDG (1.0) > D-galactose (0.84) > 3-O-methyl-glucose (0.55) > D-glucose (0.38), whereas for forward transport, specificity was: αMDG ≈ D-glucose ≈ D-galactose > 3-Omethyl-glucose. Thus there is an asymmetry in sugar kinetics and specificity between forward and reverse modes. Computer simulations showed that a 6-state kinetic model for SGLT1 can account for Na + /sugar cotransport and its voltage dependence in both the forward and reverse modes at saturating sodium concentrations. Our data indicate that under physiological conditions, the transporter is poised to accumulate sugar efficiently in the enterocyte.

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“…If this is the case, the coordination of the ions bound to NIS probably involves the same residues in both conformations. Mechanisms in which the affinities for some of the transported substrates are similar in the outwardly and the inwardly open conformations have been reported for the bacterial lactose permease (19) and Glt Ph (20). Here, we use our NIS homology model to predict and interpret the effect of mutations on transport by NIS even though, naturally, this process involves both the outwardly and the inwardly open conformations.…”

mentioning

confidence: 94%

Na ⁺ coordination at the Na2 site of the Na ⁺ /I ⁻ symporter

Ferrandino

Nicola

Sánchez

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The sodium/iodide symporter (NIS) mediates active I− transport in the thyroid—the first step in thyroid hormone biosynthesis—with a 2 Na+: 1 I− stoichiometry. The two Na+ binding sites (Na1 and Na2) and the I− binding site interact allosterically: when Na+ binds to a Na+ site, the affinity of NIS for the other Na+ and for I− increases significantly. In all Na+-dependent transporters with the same fold as NIS, the side chains of two residues, S353 and T354 (NIS numbering), were identified as the Na+ ligands at Na2. To understand the cooperativity between the substrates, we investigated the coordination at the Na2 site. We determined that four other residues—S66, D191, Q194, and Q263—are also involved in Na+ coordination at this site. Experiments in whole cells demonstrated that these four residues participate in transport by NIS: mutations at these positions result in proteins that, although expressed at the plasma membrane, transport little or no I−. These residues are conserved throughout the entire SLC5 family, to which NIS belongs, suggesting that they serve a similar function in the other transporters. Our findings also suggest that the increase in affinity that each site displays when an ion binds to another site may result from changes in the dynamics of the transporter. These mechanistic insights deepen our understanding not only of NIS but also of other transporters, including many that, like NIS, are of great medical relevance.

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Binding affinity of lactose permease is not altered by the H ⁺ electrochemical gradient

Abstract: membranes ͉ bioenergetics ͉ transport ͉ H ϩ symport ͉ membrane protein structure

Cited by 62 publications

References 42 publications

Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2

Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2

Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter

Na ⁺ coordination at the Na2 site of the Na ⁺ /I ⁻ symporter

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Binding affinity of lactose permease is not altered by the H + electrochemical gradient

Abstract: membranes ͉ bioenergetics ͉ transport ͉ H ϩ symport ͉ membrane protein structure

Cited by 62 publications

References 42 publications

Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2

Mechanistic Insights and Functional Determinants of the Transport Cycle of the Ascorbic Acid Transporter SVCT2

Kinetics of the Reverse Mode of the Na+/Glucose Cotransporter

Na + coordination at the Na2 site of the Na + /I − symporter

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Binding affinity of lactose permease is not altered by the H ⁺ electrochemical gradient

Na ⁺ coordination at the Na2 site of the Na ⁺ /I ⁻ symporter