Structure and Mechanism of a Na⁺-Independent Amino Acid Transporter
Amino acid, polyamine, and organocation (APC) transporters are secondary transporters that play essential roles in nutrient uptake, neurotransmitter recycling, ionic homeostasis, and regulation of cell volume. Here, we present the crystal structure of apo-ApcT, a proton-coupled broad-specificity ami...
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| Veröffentlicht in: | Science (American Association for the Advancement of Science) 2009-08, Vol.325 (5943), p.1010-1014 |
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| creator | Shaffer, Paul L Goehring, April Shankaranarayanan, Aruna Gouaux, Eric |
| description | Amino acid, polyamine, and organocation (APC) transporters are secondary transporters that play essential roles in nutrient uptake, neurotransmitter recycling, ionic homeostasis, and regulation of cell volume. Here, we present the crystal structure of apo-ApcT, a proton-coupled broad-specificity amino acid transporter, at 2.35 angstrom resolution. The structure contains 12 transmembrane helices, with the first 10 consisting of an inverted structural repeat of 5 transmembrane helices like the leucine transporter LeuT. The ApcT structure reveals an inward-facing, apo state and an amine moiety of lysine-158 located in a position equivalent to the sodium ion site Na2 of LeuT. We propose that lysine-158 is central to proton-coupled transport and that the amine group serves the same functional role as the Na2 ion in LeuT, thus demonstrating common principles among proton- and sodium-coupled transporters. |
| doi_str_mv | 10.1126/science.1176088 |
| format | Article |
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Here, we present the crystal structure of apo-ApcT, a proton-coupled broad-specificity amino acid transporter, at 2.35 angstrom resolution. The structure contains 12 transmembrane helices, with the first 10 consisting of an inverted structural repeat of 5 transmembrane helices like the leucine transporter LeuT. The ApcT structure reveals an inward-facing, apo state and an amine moiety of lysine-158 located in a position equivalent to the sodium ion site Na2 of LeuT. 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Psychology ; Ions ; Methanococcus - chemistry ; Models, Molecular ; Molecular biology ; Molecular biophysics ; Molecular Sequence Data ; Porters ; Protein Conformation ; Protein Folding ; Protein Structure, Secondary ; Protons ; Sodium ; Sodium - metabolism ; Structure in molecular biology ; Substrate Specificity</subject><ispartof>Science (American Association for the Advancement of Science), 2009-08, Vol.325 (5943), p.1010-1014</ispartof><rights>Copyright 2009 American Association for the Advancement of Science</rights><rights>2009 INIST-CNRS</rights><rights>Copyright © 2009, American Association for the Advancement of Science</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c653t-53a087c57a43f60eaea4db0e69ffc4df1ca3fea76e7eca40a400b11957a721a83</citedby><cites>FETCH-LOGICAL-c653t-53a087c57a43f60eaea4db0e69ffc4df1ca3fea76e7eca40a400b11957a721a83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/20544369$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/20544369$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,780,784,803,885,2882,2883,27922,27923,58015,58248</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21845829$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19608859$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shaffer, Paul L</creatorcontrib><creatorcontrib>Goehring, April</creatorcontrib><creatorcontrib>Shankaranarayanan, Aruna</creatorcontrib><creatorcontrib>Gouaux, Eric</creatorcontrib><title>Structure and Mechanism of a Na⁺-Independent Amino Acid Transporter</title><title>Science (American Association for the Advancement of Science)</title><addtitle>Science</addtitle><description>Amino acid, polyamine, and organocation (APC) transporters are secondary transporters that play essential roles in nutrient uptake, neurotransmitter recycling, ionic homeostasis, and regulation of cell volume. 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Psychology</subject><subject>Ions</subject><subject>Methanococcus - chemistry</subject><subject>Models, Molecular</subject><subject>Molecular biology</subject><subject>Molecular biophysics</subject><subject>Molecular Sequence Data</subject><subject>Porters</subject><subject>Protein Conformation</subject><subject>Protein Folding</subject><subject>Protein Structure, Secondary</subject><subject>Protons</subject><subject>Sodium</subject><subject>Sodium - metabolism</subject><subject>Structure in molecular biology</subject><subject>Substrate Specificity</subject><issn>0036-8075</issn><issn>1095-9203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAQhi0EokvhzAmIkOAWOrZjx74graoClQoc2p6tWcdps0rsxU6QOPJaPE6fpI42aoFLJcvW6P_m13h-Ql5S-EApk0fJds5bl4taglKPyIqCFqVmwB-TFQCXpYJaHJBnKW0Bsqb5U3JA9UwLvSIn52Oc7DhFV6Bviq_OXqPv0lCEtsDiG978_lOe-sbtXL78WKyHzodibbumuIjo0y7E0cXn5EmLfXIvlveQXH46uTj-Up59_3x6vD4rrRR8LAVHULUVNVa8leDQYdVswEndtrZqWmqRtw5r6WpnsYJ8YEOpzg01o6j4Ifm4991Nm8E1Nk8UsTe72A0Yf5mAnflX8d21uQo_DVOCioplg_eLQQw_JpdGM3TJur5H78KUjKyFVhXUD4JcMiGoUg-CLM-vKyoy-PY_cBum6PO6MsMlABPzfEd7yMaQUnTt3d8omDlxsyRulsRzx-u_V3LPLxFn4N0CYLLYtzk126U7jlFVCcVm7tWe26YxxHsdRFVxOetv9nqLweBVzB6X5wwoByqlphr4LR5kyQ0</recordid><startdate>20090821</startdate><enddate>20090821</enddate><creator>Shaffer, Paul L</creator><creator>Goehring, April</creator><creator>Shankaranarayanan, Aruna</creator><creator>Gouaux, Eric</creator><general>American Association for the Advancement of Science</general><general>The American Association for the Advancement of Science</general><scope>FBQ</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QQ</scope><scope>7QR</scope><scope>7SC</scope><scope>7SE</scope><scope>7SN</scope><scope>7SP</scope><scope>7SR</scope><scope>7SS</scope><scope>7T7</scope><scope>7TA</scope><scope>7TB</scope><scope>7TK</scope><scope>7TM</scope><scope>7U5</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>K9.</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7ST</scope><scope>7TV</scope><scope>7U6</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090821</creationdate><title>Structure and Mechanism of a Na⁺-Independent Amino Acid Transporter</title><author>Shaffer, Paul L ; Goehring, April ; Shankaranarayanan, Aruna ; Gouaux, Eric</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c653t-53a087c57a43f60eaea4db0e69ffc4df1ca3fea76e7eca40a400b11957a721a83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Amines</topic><topic>Amino Acid Sequence</topic><topic>Amino acid transport systems</topic><topic>Amino Acid Transport Systems - chemistry</topic><topic>Amino Acid Transport Systems - metabolism</topic><topic>Amino acids</topic><topic>Amino Acids - metabolism</topic><topic>Antiporters</topic><topic>Antiporters - chemistry</topic><topic>Apoproteins - chemistry</topic><topic>Apoproteins - metabolism</topic><topic>Archaeal Proteins - chemistry</topic><topic>Archaeal Proteins - metabolism</topic><topic>Biochemistry</topic><topic>Biological and medical sciences</topic><topic>Crystal structure</topic><topic>Crystalline structure</topic><topic>Crystallization</topic><topic>Crystallography, X-Ray</topic><topic>Epithelial cells</topic><topic>Escherichia coli Proteins - chemistry</topic><topic>Fundamental and applied biological sciences. 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| subjects | Amines Amino Acid Sequence Amino acid transport systems Amino Acid Transport Systems - chemistry Amino Acid Transport Systems - metabolism Amino acids Amino Acids - metabolism Antiporters Antiporters - chemistry Apoproteins - chemistry Apoproteins - metabolism Archaeal Proteins - chemistry Archaeal Proteins - metabolism Biochemistry Biological and medical sciences Crystal structure Crystalline structure Crystallization Crystallography, X-Ray Epithelial cells Escherichia coli Proteins - chemistry Fundamental and applied biological sciences. Psychology Ions Methanococcus - chemistry Models, Molecular Molecular biology Molecular biophysics Molecular Sequence Data Porters Protein Conformation Protein Folding Protein Structure, Secondary Protons Sodium Sodium - metabolism Structure in molecular biology Substrate Specificity |
| title | Structure and Mechanism of a Na⁺-Independent Amino Acid Transporter |
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