Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity

Alguel, Yilmaz; Amillis, Sotiris; Leung, James; Lambrinidis, George; Capaldi, Stefano; Scull, Nicola J.; Craven, Gregory B.; Iwata, So; Armstrong, Alan; Mikros, Emmanuel; Diallinas, George; Cameron, Alexander D.; Byrne, Bernadette

doi:10.1038/ncomms11336

Cited by 122 publications

(251 citation statements)

References 55 publications

(92 reference statements)

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“…Each Bor1 monomer recapitulates a fold seen in Band 3 (24), and in the more distantly related nucleobase-ascorbate transporter (NAT) proteins UraA and UapA (27,28). Additionally, the SLC26 family has been observed to display the same overall fold, as shown in a recent structure of SLC26Dg (29).…”

Section: Significancementioning

confidence: 67%

“…There is no ligand bound in our structure, but as in the case with Band 3 (24), UraA (27), UapA (28), and SLC26Dg (29), the substrate-binding site likely resides where the ends of the shortened TM helices TM3 and TM10 pass each other. Although our model was improved by keeping most side chains present, the resolution precludes commenting specifically on their conformations and contacts.…”

Section: Significancementioning

confidence: 83%

“…The difference between an elevator transporter mechanism and a rocking-bundle (32). The NAT transporter UapA has been proposed to function as an elevator transporter (28). Bor1, and the SLC4 family in general, also appear to meet these requirements.…”

Section: Discussionmentioning

confidence: 99%

“…Whereas the Band 3 structure was determined in an outward-open state, NAT transporters UapA and UraA were determined in inward-open states with substrates bound (27,28). Superposition of the TMs of the Gate domains of Bor1 and UapA shows a reasonably close alignment, with a Cα rmsd of 3.1 Å (Fig.…”

Section: Significancementioning

confidence: 97%

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Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers

Thurtle‐Schmidt

Stroud

2016

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

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Boron is essential for plant growth because of its incorporation into plant cell walls; however, in excess it is toxic to plants. Boron transport and homeostasis in plants is regulated in part by the borate efflux transporter Bor1, a member of the solute carrier (SLC) 4 transporter family with homology to the human bicarbonate transporter Band 3. Here, we present the 4.1-Å resolution crystal structure of Arabidopsis thaliana Bor1. The structure displays a dimeric architecture in which dimerization is mediated by centralized Gate domains. Comparisons with a structure of Band 3 in an outward-open state reveal that the Core domains of Bor1 have rotated inwards to achieve an occluded state. Further structural comparisons with UapA, a xanthine transporter from the nucleobase-ascorbate transporter family, show that the downward pivoting of the Core domains relative to the Gate domains may access an inward-open state. These results suggest that the SLC4, SLC26, and nucleobase-ascorbate transporter families all share an elevator transport mechanism in which alternating access is provided by Core domains that carry substrates across a membrane.T he defining feature of transporters is the ability to carry specific molecules across a membrane. The solute carrier (SLC) group comprises a diverse array of transporters grouped into at least 52 families based on function and sequence homology (1). The SLC4 family is termed the bicarbonate transporters and is subdivided into sodium-coupled cotransporters and anion exchanger subclasses. The SLC4 anion exchangers transport ions in an electroneutral manner, most commonly transporting bicarbonate in exchange for chloride. In addition to bicarbonate transporters, the SLC4 transporters include borate efflux transporters, originally discovered in plants (2, 3). Boron is an essential plant micronutrient that is taken up from the soil and participates in the formation of esters found in plant cell walls. Specifically, borate diesters cross-link a primary cell wall component, pectic polysaccharide rhamnogalacturonan II (RG-II) and, thus, contribute to plant cell wall stability (4, 5). In excess levels, however, boron is toxic to plants. The regulation of boron by transporters is therefore important for plant viability and has implications for worldwide agriculture. Indeed, there are ongoing efforts to engineer plants that are tolerant of either high or low boron levels in soil (6-8). The transport and regulation of boron levels is regulated partly by Bor1, a boron exporter that loads xylem, such that boron is transported from roots to shoots and leaves (3). The precise chemical nature boron takes during transport is not known, but is commonly assumed to be borate, an anionic form of boric acid. Bor1 is active in plants under limiting borate conditions, but is degraded under high concentrations of borate to avoid accumulation of toxic boron levels in plant shoots (9). Although the transporter function and regulation of Bor1 in response to excess borate have been defined, the mechanism by w...

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Section: Significancementioning

confidence: 67%

Section: Significancementioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 97%

See 2 more Smart Citations

Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers

Thurtle‐Schmidt

Stroud

2016

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

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“…Intriguingly, dimer formation appears to be essential for transport activity, however, co-expression of wild-type UraA with a nonfunctional mutant does not affect the activity indicating a lack of functional interdependency of the two protomers. This is in contrast to the related uric acid/xanthine transporter, from Aspergillus nidulans, UapA [7]. In this case, studies of dominant negative mutants reveal that one UapA protomer affects the overall transport activity of the associated molecule.…”

mentioning

confidence: 82%

It takes two to transport via an elevator

Byrne

2017

Cell Res

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The solute transport and binding profile of a novel nucleobase cation symporter 2 from the honeybee pathogen Paenibacillus larvae

et al. 2018

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Here, we report that a novel nucleobase cation symporter 2 encoded in the genome of the honeybee bacterial pathogen Paenibacillus larvae reveals high levels of amino acid sequence similarity to the Escherichia coli and Bacillus subtilis uric acid and xanthine transporters. This transporter is named P. larvae uric acid permease‐like protein (PlUacP). Even though PlUacP displays overall amino acid sequence similarities, has common secondary structures, and shares functional motifs and functionally important amino acids with E. coli xanthine and uric acid transporters, these commonalities are insufficient to assign transport function to PlUacP. The solute transport and binding profile of PlUacP was determined by radiolabeled uptake experiments via heterologous expression in nucleobase transporter‐deficient Saccharomyces cerevisiae strains. PlUacP transports the purines adenine and guanine and the pyrimidine uracil. Hypoxanthine, xanthine, and cytosine are not transported by PlUacP, but, along with uric acid, bind in a competitive manner. PlUacP has strong affinity for adenine K m 7.04 ± 0.18 μ m , and as with other bacterial and plant NCS 2 proteins, PlUacP function is inhibited by the proton disruptor carbonyl cyanide m‐chlorophenylhydrazone. The solute transport and binding profile identifies PlUacP as a novel nucleobase transporter.

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Structure of eukaryotic purine/H+ symporter UapA suggests a role for homodimerization in transport activity

Cited by 122 publications

References 55 publications

Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers

Structure of Bor1 supports an elevator transport mechanism for SLC4 anion exchangers

It takes two to transport via an elevator

The solute transport and binding profile of a novel nucleobase cation symporter 2 from the honeybee pathogen Paenibacillus larvae

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