ArticleThe Journal of general physiology2001
Cysteine mutagenesis reveals novel structure-function features within the predicted third extracellular loop of the type IIa Na(+)/P(i) cotransporter.
Article in The Journal of general physiology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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26 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- New insights in the genetic variant spectrum of SLC34A2 in pulmonary alveolar microlithiasis; a systematic review.Orphanet journal of rare diseases · 2023Pooled it
- Impaired phosphate transport in SLC34A2 variants in patients with pulmonary alveolar microlithiasis.Human genomics · 2022Article
- The molecular mechanism of SLC34 proteins: insights from two decades of transport assays and structure-function studies.Pflugers Archiv : European journal of physiology · 2019Review
- Structural models of the NaPi-II sodium-phosphate cotransporters.Pflugers Archiv : European journal of physiology · 2019Review
- Identification of the first sodium binding site of the phosphate cotransporter NaPi-IIa (SLC34A1).Biophysical journal · 2015Article
- Structural fold and binding sites of the human Na⁺-phosphate cotransporter NaPi-II.Biophysical journal · 2014Article
- The SLC34 family of sodium-dependent phosphate transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Conferring electrogenicity to the electroneutral phosphate cotransporter NaPi-IIc (SLC34A3) reveals an internal cation release step.Pflugers Archiv : European journal of physiology · 2013Article
- Molecular cloning and functional characterization of swine sodium dependent phosphate cotransporter type II b (NaPi-IIb) gene.Molecular biology reports · 2012Article
- Voltage- and substrate-dependent interactions between sites in putative re-entrant domains of a Na(+)-coupled phosphate cotransporter.Pflugers Archiv : European journal of physiology · 2011Article
- Substrate interactions of the electroneutral Na+-coupled inorganic phosphate cotransporter (NaPi-IIc).The Journal of physiology · 2009Article
- Alteration of sugar-induced conformational changes of the melibiose permease by mutating Arg141 in loop 4-5.Biophysical journal · 2009Article
- Residues accessible in the binding-site crevice of transmembrane helix 6 of the CB2 cannabinoid receptor.Biochemistry · 2008Article
- Oligomeric structure and minimal functional unit of the electrogenic sodium bicarbonate cotransporter NBCe1-A.The Journal of biological chemistry · 2008Article
- Genetic dissection of the divergent activities of the multifunctional membrane sensor BglF.Journal of bacteriology · 2007Article
- Voltage clamp fluorometric measurements on a type II Na+-coupled Pi cotransporter: shedding light on substrate binding order.The Journal of general physiology · 2006Article
- Identification of a disulfide bridge linking the fourth and the seventh extracellular loops of the Na+/glucose cotransporter.The Journal of general physiology · 2006Article
- Electrogenic kinetics of a mammalian intestinal type IIb Na(+)/P(i) cotransporter.The Journal of membrane biology · 2006Article
- Topology of the type IIa Na+/P(i) cotransporter.The Journal of membrane biology · 2006Article
- The 2-hydroxycarboxylate transporter family: physiology, structure, and mechanism.Microbiology and molecular biology reviews : MMBR · 2005Review
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6 authors at 1 institution in 1 country.
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Abstract
The transport function of the rat type IIa Na(+)/P(i) cotransporter is inhibited after binding the cysteine modifying reagent 2-aminoethyl methanethiosulfonate hydrobromide (MTSEA) to a cysteine residue substituted for a serine at position 460 (S460C) in the predicted third extracellular loop. This suggests that Ser-460 lies in a functionally important region of the protein. To establish a "structure-function" profile for the regions that flank Ser-460, the substituted cysteine accessibility method was employed. 18 mutants were constructed in which selected amino acids from Arg-437 through Leu-465 were substituted one by one for a cysteine. Mutants were expressed in Xenopus oocytes and transport function (cotransport and slippage) and kinetics were assayed by electrophysiology with or without prior treatment with cysteine modifying (methanethiosulfonate, MTS) reagents. Except for mutant I447C, mutants with cysteines at sites from Arg-437 through Thr-449, as well as Pro-461, were inactive. Cotransport function of mutants with Cys substitutions at sites Arg-462 through Leu-465 showed low sensitivity to MTS reagents. The preceding mutants (Cys substitution at Thr-451 to Ser-460) showed a periodic accessibility pattern that would be expected for an alpha-helix motif. Apart from loss of transport function, exposure of mutants A453C and A455C to MTSEA or 2-(triethylammonium)ethyl MTS bromide (MTSET) increased the uncoupled slippage current, which implicated the mutated sites in the leak pathway. Mutants from Ala-453 through Ala-459 showed less pH dependency, but generally stronger voltage dependency compared with the wild type, whereas those flanking this group were more sensitive to pH and showed weaker voltage dependence of cotransport mode kinetics. Our data indicate that parts of the third extracellular loop are involved in the translocation of the fully loaded carrier and show a membrane-associated alpha-helical structure.
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