2l0e

From Proteopedia

(Difference between revisions)

Current revision

Structural and functional analysis of tm vi of the nhe1 isoform of the na+/h+ exchanger

Structural highlights

2l0e is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR, 40 models
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The Na+/H+ exchanger isoform 1 is a ubiquitously expressed integral membrane protein. It resides on the plasma membrane of cells and regulates intracellular pH in mammals by extruding an intracellular H+ in exchange for one extracellular Na+. We characterized structural and functional aspects of the transmembrane (TM) segment VI (residues 227-249) by using cysteine scanning mutagenesis and high resolution NMR. Each residue of TM VI was mutated to cysteine in the background of the cysteineless NHE1 protein and the sensitivity to water soluble sulfhydryl reactive compounds MTSET ([2- (Trimethylammonium) Ethyl]Methanethiosulfonate) and MTSES ([2-Sulfonatoethyl]Methanethiosulfonate) was determined for those residues with significant activity remaining. Three residues were essentially inactive when mutated to Cys, Asp238, Pro239 and Glu247. Of the remaining residues, proteins with the mutations N227C, I233C, and L243C were strongly inhibited by MTSET while amino acids Phe230, Gly231, Aal236, Val237, Ala244, Val245 and Glu248 were partially inhibited by MTSET. MTSES did not affect activity of the mutant NHE1 proteins. The structure of a peptide representing TM VI was determined using high resolution NMR spectroscopy in dodecylphosphocholine (DPC) micelles. TM VI contains two helical regions oriented at an approximate right angle to each other (residues 229-236 and 239-250) surrounding a central unwound region. This structure bares a resemblance to TM IV of the E. coli protein NhaA. The results demonstrate that TM VI of NHE1 is a discontinuous pore lining helix with residues Asn227, Ile233 and Leu243 lining the translocation pore.

Structural and functional analysis of transmembrane VI of the NHE1 isoform of the Na+/H+ exchanger.,Tzeng J, Lee BL, Sykes BD, Fliegel L J Biol Chem. 2010 Sep 15. PMID:20843797^[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
↑ Tzeng J, Lee BL, Sykes BD, Fliegel L. Structural and functional analysis of transmembrane VI of the NHE1 isoform of the Na+/H+ exchanger. J Biol Chem. 2010 Sep 15. PMID:20843797 doi:10.1074/jbc.M110.161471

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l0e"

@@ Line 1: / Line 1: @@
 ==Structural and functional analysis of tm vi of the nhe1 isoform of the na+/h+ exchanger==
-<StructureSection load='2l0e' size='340' side='right'caption='[[2l0e]], [[NMR_Ensembles_of_Models | 40 NMR models]]' scene=''>
+<StructureSection load='2l0e' size='340' side='right'caption='[[2l0e]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2l0e]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L0E FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2l0e]] 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=2L0E OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L0E FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 40 models</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2l0e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l0e OCA], [https://pdbe.org/2l0e PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l0e RCSB], [https://www.ebi.ac.uk/pdbsum/2l0e PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l0e ProSAT]</span></td></tr>
 </table>
 == 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>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 14: / Line 15: @@
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/l0/2l0e_consurf.spt"</scriptWhenChecked>
-    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
@@ Line 32: / Line 33: @@
 __TOC__
 </StructureSection>
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Fliegel, L]]
+[[Category: Fliegel L]]
-[[Category: Lee, B L]]
+[[Category: Lee BL]]
-[[Category: Sykes, B D]]
+[[Category: Sykes BD]]
-[[Category: Tzeng, J]]
+[[Category: Tzeng J]]
-[[Category: Membrane protein]]
-[[Category: Nhe1]]
-[[Category: Transmembrane helix]]

2l0e

From Proteopedia

Current revision

Structural and functional analysis of tm vi of the nhe1 isoform of the na+/h+ exchanger

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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