9l1d: Difference between revisions

Latest revision as of 09:22, 15 April 2026

Structure of piperidine-4-sulfonic acid-bound human Taurine Transporter in the inward-open conformation

Structural highlights

9l1d is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.24Å
Ligands:	A1EBD, CL, Y01
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SC6A6_HUMAN The disease is caused by variants affecting the gene represented in this entry.

Function

SC6A6_HUMAN Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Can also mediate transport of hypotaurine and gamma-aminobutyric acid (GABA) (By similarity).[UniProtKB:O35316]^[1] ^[2] ^[3] ^[4] ^[5] Sodium-dependent taurine and beta-alanine transporter. Chloride ions are necessary for optimal uptake.^[6] ^[7] ^[8]

Publication Abstract from PubMed

Taurine is a sulfur-containing amino acid that plays several crucial roles in the body. Its uptake is mediated by the taurine transporter (TauT). Genetic mutations and dysregulation of TauT have been linked to various neurological disorders, cardiomyopathy, childhood progressive retinal degeneration, and cancer, making TauT a promising target for therapeutic intervention in these diseases. However, the structure and mechanism of TauT remain poorly understood. In this study, we present the structures of the human taurine transporter (hTauT) under four conditions: the substrate-free state, the taurine-bound state, the beta-alanine-bound state, and the cyclic inhibitor piperidine-4-sulfonate (P4S)-bound state. These structures reveal that taurine binds at the central substrate-binding site of hTauT. Notably, beta-alanine and the cyclic P4S inhibitors also mimic taurine, occupying the same substrate-binding site. In the substrate-free and P4S-bound forms, hTauT also adopt an inward-open conformation, where transmembrane helix TM1a bends toward the membrane, facilitating the opening of the intracellular gate for ion and substrate release. These structural insights enhance our understanding of the mechanisms underlying substrate and ion recognition and transport in hTauT, paving the way for the future development of taurine transporter substrate analogues or selective inhibitors.

Structural mechanism of substrate binding and inhibition of human taurine transporter.,Qi Y, Zhang Y, Wang D, Liu J, Zhou Y, Ji W, Chen X, Liu L, Wang R, Wu JX Nat Commun. 2026 Mar 20. doi: 10.1038/s41467-026-70772-x. PMID:41857056^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Preising MN, Görg B, Friedburg C, Qvartskhava N, Budde BS, Bonus M, Toliat MR, Pfleger C, Altmüller J, Herebian D, Beyer M, Zöllner HJ, Wittsack HJ, Schaper J, Klee D, Zechner U, Nürnberg P, Schipper J, Schnitzler A, Gohlke H, Lorenz B, Häussinger D, Bolz HJ. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration. FASEB J. 2019 Oct;33(10):11507-11527. PMID:31345061 doi:10.1096/fj.201900914RR
↑ Ansar M, Ranza E, Shetty M, Paracha SA, Azam M, Kern I, Iwaszkiewicz J, Farooq O, Pournaras CJ, Malcles A, Kecik M, Rivolta C, Muzaffar W, Qurban A, Ali L, Aggoun Y, Santoni FA, Makrythanasis P, Ahmed J, Qamar R, Sarwar MT, Henry LK, Antonarakis SE. Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency. Hum Mol Genet. 2020 Mar 13;29(4):618-623. PMID:31903486 doi:10.1093/hmg/ddz303
↑ Ramamoorthy S, Leibach FH, Mahesh VB, Han H, Yang-Feng T, Blakely RD, Ganapathy V. Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J. 1994 Jun 15;300 ( Pt 3)(Pt 3):893-900. PMID:8010975 doi:10.1042/bj3000893
↑ Jhiang SM, Fithian L, Smanik P, McGill J, Tong Q, Mazzaferri EL. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 1993 Mar 1;318(2):139-44. PMID:8382624 doi:10.1016/0014-5793(93)80008-i
↑ Miyamoto Y, Liou GI, Sprinkle TJ. Isolation of a cDNA encoding a taurine transporter in the human retinal pigment epithelium. Curr Eye Res. 1996 Mar;15(3):345-9. PMID:8654117 doi:10.3109/02713689609007631
↑ Preising MN, Görg B, Friedburg C, Qvartskhava N, Budde BS, Bonus M, Toliat MR, Pfleger C, Altmüller J, Herebian D, Beyer M, Zöllner HJ, Wittsack HJ, Schaper J, Klee D, Zechner U, Nürnberg P, Schipper J, Schnitzler A, Gohlke H, Lorenz B, Häussinger D, Bolz HJ. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration. FASEB J. 2019 Oct;33(10):11507-11527. PMID:31345061 doi:10.1096/fj.201900914RR
↑ Ansar M, Ranza E, Shetty M, Paracha SA, Azam M, Kern I, Iwaszkiewicz J, Farooq O, Pournaras CJ, Malcles A, Kecik M, Rivolta C, Muzaffar W, Qurban A, Ali L, Aggoun Y, Santoni FA, Makrythanasis P, Ahmed J, Qamar R, Sarwar MT, Henry LK, Antonarakis SE. Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency. Hum Mol Genet. 2020 Mar 13;29(4):618-623. PMID:31903486 doi:10.1093/hmg/ddz303
↑ Jhiang SM, Fithian L, Smanik P, McGill J, Tong Q, Mazzaferri EL. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 1993 Mar 1;318(2):139-44. PMID:8382624 doi:10.1016/0014-5793(93)80008-i
↑ Qi Y, Zhang Y, Wang D, Liu J, Zhou Y, Ji W, Chen X, Liu L, Wang R, Wu JX. Structural mechanism of substrate binding and inhibition of human taurine transporter. Nat Commun. 2026 Mar 20. PMID:41857056 doi:10.1038/s41467-026-70772-x

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Preising MN, Görg B, Friedburg C, Qvartskhava N, Budde BS, Bonus M, Toliat MR, Pfleger C, Altmüller J, Herebian D, Beyer M, Zöllner HJ, Wittsack HJ, Schaper J, Klee D, Zechner U, Nürnberg P, Schipper J, Schnitzler A, Gohlke H, Lorenz B, Häussinger D, Bolz HJ. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration. FASEB J. 2019 Oct;33(10):11507-11527. PMID:31345061 doi:10.1096/fj.201900914RR

[2] Ansar M, Ranza E, Shetty M, Paracha SA, Azam M, Kern I, Iwaszkiewicz J, Farooq O, Pournaras CJ, Malcles A, Kecik M, Rivolta C, Muzaffar W, Qurban A, Ali L, Aggoun Y, Santoni FA, Makrythanasis P, Ahmed J, Qamar R, Sarwar MT, Henry LK, Antonarakis SE. Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency. Hum Mol Genet. 2020 Mar 13;29(4):618-623. PMID:31903486 doi:10.1093/hmg/ddz303

[3] Ramamoorthy S, Leibach FH, Mahesh VB, Han H, Yang-Feng T, Blakely RD, Ganapathy V. Functional characterization and chromosomal localization of a cloned taurine transporter from human placenta. Biochem J. 1994 Jun 15;300 ( Pt 3)(Pt 3):893-900. PMID:8010975 doi:10.1042/bj3000893

[4] Jhiang SM, Fithian L, Smanik P, McGill J, Tong Q, Mazzaferri EL. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 1993 Mar 1;318(2):139-44. PMID:8382624 doi:10.1016/0014-5793(93)80008-i

[5] Miyamoto Y, Liou GI, Sprinkle TJ. Isolation of a cDNA encoding a taurine transporter in the human retinal pigment epithelium. Curr Eye Res. 1996 Mar;15(3):345-9. PMID:8654117 doi:10.3109/02713689609007631

[6] Preising MN, Görg B, Friedburg C, Qvartskhava N, Budde BS, Bonus M, Toliat MR, Pfleger C, Altmüller J, Herebian D, Beyer M, Zöllner HJ, Wittsack HJ, Schaper J, Klee D, Zechner U, Nürnberg P, Schipper J, Schnitzler A, Gohlke H, Lorenz B, Häussinger D, Bolz HJ. Biallelic mutation of human SLC6A6 encoding the taurine transporter TAUT is linked to early retinal degeneration. FASEB J. 2019 Oct;33(10):11507-11527. PMID:31345061 doi:10.1096/fj.201900914RR

[7] Ansar M, Ranza E, Shetty M, Paracha SA, Azam M, Kern I, Iwaszkiewicz J, Farooq O, Pournaras CJ, Malcles A, Kecik M, Rivolta C, Muzaffar W, Qurban A, Ali L, Aggoun Y, Santoni FA, Makrythanasis P, Ahmed J, Qamar R, Sarwar MT, Henry LK, Antonarakis SE. Taurine treatment of retinal degeneration and cardiomyopathy in a consanguineous family with SLC6A6 taurine transporter deficiency. Hum Mol Genet. 2020 Mar 13;29(4):618-623. PMID:31903486 doi:10.1093/hmg/ddz303

[8] Jhiang SM, Fithian L, Smanik P, McGill J, Tong Q, Mazzaferri EL. Cloning of the human taurine transporter and characterization of taurine uptake in thyroid cells. FEBS Lett. 1993 Mar 1;318(2):139-44. PMID:8382624 doi:10.1016/0014-5793(93)80008-i

[9] Qi Y, Zhang Y, Wang D, Liu J, Zhou Y, Ji W, Chen X, Liu L, Wang R, Wu JX. Structural mechanism of substrate binding and inhibition of human taurine transporter. Nat Commun. 2026 Mar 20. PMID:41857056 doi:10.1038/s41467-026-70772-x

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[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 9l1d is ON HOLD  until Paper Publication
+==Structure of piperidine-4-sulfonic acid-bound human Taurine Transporter in the inward-open conformation==
+<StructureSection load='9l1d' size='340' side='right'caption='[[9l1d]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[9l1d]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9L1D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9L1D FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.24&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1EBD:piperidine-4-sulfonic+acid'>A1EBD</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</scene></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9l1d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9l1d OCA], [https://pdbe.org/9l1d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9l1d RCSB], [https://www.ebi.ac.uk/pdbsum/9l1d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9l1d ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/SC6A6_HUMAN SC6A6_HUMAN] The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/SC6A6_HUMAN SC6A6_HUMAN] Mediates sodium- and chloride-dependent transport of taurine (PubMed:31345061, PubMed:31903486, PubMed:8010975, PubMed:8382624, PubMed:8654117). Mediates transport of beta-alanine (PubMed:8010975). Can also mediate transport of hypotaurine and gamma-aminobutyric acid (GABA) (By similarity).[UniProtKB:O35316]<ref>PMID:31345061</ref> <ref>PMID:31903486</ref> <ref>PMID:8010975</ref> <ref>PMID:8382624</ref> <ref>PMID:8654117</ref>   Sodium-dependent taurine and beta-alanine transporter. Chloride ions are necessary for optimal uptake.<ref>PMID:31345061</ref> <ref>PMID:31903486</ref> <ref>PMID:8382624</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Taurine is a sulfur-containing amino acid that plays several crucial roles in the body. Its uptake is mediated by the taurine transporter (TauT). Genetic mutations and dysregulation of TauT have been linked to various neurological disorders, cardiomyopathy, childhood progressive retinal degeneration, and cancer, making TauT a promising target for therapeutic intervention in these diseases. However, the structure and mechanism of TauT remain poorly understood. In this study, we present the structures of the human taurine transporter (hTauT) under four conditions: the substrate-free state, the taurine-bound state, the beta-alanine-bound state, and the cyclic inhibitor piperidine-4-sulfonate (P4S)-bound state. These structures reveal that taurine binds at the central substrate-binding site of hTauT. Notably, beta-alanine and the cyclic P4S inhibitors also mimic taurine, occupying the same substrate-binding site. In the substrate-free and P4S-bound forms, hTauT also adopt an inward-open conformation, where transmembrane helix TM1a bends toward the membrane, facilitating the opening of the intracellular gate for ion and substrate release. These structural insights enhance our understanding of the mechanisms underlying substrate and ion recognition and transport in hTauT, paving the way for the future development of taurine transporter substrate analogues or selective inhibitors.
-Authors:
+Structural mechanism of substrate binding and inhibition of human taurine transporter.,Qi Y, Zhang Y, Wang D, Liu J, Zhou Y, Ji W, Chen X, Liu L, Wang R, Wu JX Nat Commun. 2026 Mar 20. doi: 10.1038/s41467-026-70772-x. PMID:41857056<ref>PMID:41857056</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 9l1d" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Qi Y]]
+[[Category: Wu JX]]

9l1d: Difference between revisions

Latest revision as of 09:22, 15 April 2026

Structure of piperidine-4-sulfonic acid-bound human Taurine Transporter in the inward-open conformation

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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