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| | ==NMR structure of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger== | | ==NMR structure of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger== |
| - | <StructureSection load='1y4e' size='340' side='right'caption='[[1y4e]], [[NMR_Ensembles_of_Models | 100 NMR models]]' scene=''> | + | <StructureSection load='1y4e' size='340' side='right'caption='[[1y4e]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1y4e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y4E FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1y4e]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y4E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Y4E FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SLC9A1, APNH1, NHE1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</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=1y4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y4e OCA], [https://pdbe.org/1y4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y4e RCSB], [https://www.ebi.ac.uk/pdbsum/1y4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y4e ProSAT]</span></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=1y4e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1y4e OCA], [https://pdbe.org/1y4e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1y4e RCSB], [https://www.ebi.ac.uk/pdbsum/1y4e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1y4e ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/SL9A1_HUMAN SL9A1_HUMAN]] Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.<ref>PMID:8901634</ref> <ref>PMID:11350981</ref> <ref>PMID:15035633</ref>
| + | [https://www.uniprot.org/uniprot/SL9A1_HUMAN SL9A1_HUMAN] Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.<ref>PMID:8901634</ref> <ref>PMID:11350981</ref> <ref>PMID:15035633</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fliegel, L]] | + | [[Category: Fliegel L]] |
| - | [[Category: Li, X]] | + | [[Category: Li X]] |
| - | [[Category: Lindhout, D A]] | + | [[Category: Lindhout DA]] |
| - | [[Category: Liu, Y]] | + | [[Category: Liu Y]] |
| - | [[Category: Rainey, J K]] | + | [[Category: Rainey JK]] |
| - | [[Category: Slepkov, E R]] | + | [[Category: Slepkov ER]] |
| - | [[Category: Sykes, B D]] | + | [[Category: Sykes BD]] |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Nhe1 isoform]]
| + | |
| - | [[Category: Transmembrane]]
| + | |
| Structural highlights
Function
SL9A1_HUMAN Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction.[1] [2] [3]
Publication Abstract from PubMed
The Na(+)/H(+) exchanger isoform 1 is a ubiquitously expressed integral membrane protein that regulates intracellular pH in mammals. We characterized the structural and functional aspects of the critical transmembrane (TM) segment IV. Each residue was mutated to cysteine in cysteine-less NHE1. TM IV was exquisitely sensitive to mutation with 10 of 23 mutations causing greatly reduced expression and/or activity. The Phe(161) --> Cys mutant was inhibited by treatment with the water-soluble sulfhydryl-reactive compounds [2-(trimethylammonium)ethyl]methanethiosulfonate and [2-sulfonatoethyl]methanethiosulfonate, suggesting it is a pore-lining residue. The structure of purified TM IV peptide was determined using high resolution NMR in a CD(3)OH:CDCl(3):H(2)O mixture and in Me(2)SO. In CD(3)OH: CDCl(3):H(2)O, TM IV was structured but not as a canonical alpha-helix. Residues Asp(159)-Leu(162) were a series of beta-turns; residues Leu(165)-Pro(168) showed an extended structure, and residues Ile(169)-Phe(176) were helical in character. These three structured regions rotated quite freely with respect to the others. In Me(2)SO, the structure was much less defined. Our results demonstrate that TM IV is an unusually structured transmembrane segment that is exquisitely sensitive to mutagenesis and that Phe(161) is a pore-lining residue.
Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger.,Slepkov ER, Rainey JK, Li X, Liu Y, Cheng FJ, Lindhout DA, Sykes BD, Fliegel L J Biol Chem. 2005 May 6;280(18):17863-72. Epub 2005 Jan 26. PMID:15677483[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin X, Barber DL. A calcineurin homologous protein inhibits GTPase-stimulated Na-H exchange. Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12631-6. PMID:8901634
- ↑ Pang T, Su X, Wakabayashi S, Shigekawa M. Calcineurin homologous protein as an essential cofactor for Na+/H+ exchangers. J Biol Chem. 2001 May 18;276(20):17367-72. Epub 2001 Feb 28. PMID:11350981 doi:http://dx.doi.org/10.1074/jbc.M100296200
- ↑ Pang T, Hisamitsu T, Mori H, Shigekawa M, Wakabayashi S. Role of calcineurin B homologous protein in pH regulation by the Na+/H+ exchanger 1: tightly bound Ca2+ ions as important structural elements. Biochemistry. 2004 Mar 30;43(12):3628-36. PMID:15035633 doi:http://dx.doi.org/10.1021/bi0360004
- ↑ Slepkov ER, Rainey JK, Li X, Liu Y, Cheng FJ, Lindhout DA, Sykes BD, Fliegel L. Structural and functional characterization of transmembrane segment IV of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem. 2005 May 6;280(18):17863-72. Epub 2005 Jan 26. PMID:15677483 doi:http://dx.doi.org/M409608200
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