View source for 2htg


==Structural and functional characterization of TM VII of the NHE1 isoform of the Na+/H+ exchanger==
<StructureSection load='2htg' size='340' side='right'caption='[[2htg]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2htg]] 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=2HTG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HTG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 66 models</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=2htg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2htg OCA], [https://pdbe.org/2htg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2htg RCSB], [https://www.ebi.ac.uk/pdbsum/2htg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2htg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O08938_MERUN O08938_MERUN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The Na(+)/H(+) exchanger isoform 1 is an integral membrane protein that regulates intracellular pH by exchanging one intracellular H(+) for one extracellular Na(+). It is composed of an N-terminal membrane domain of 12 transmembrane segments and an intracellular C-terminal regulatory domain. We characterized the structural and functional aspects of the critical transmembrane segment VII (TM VII, residues 251-273) by using alanine scanning mutagenesis and high resolution NMR. Each residue of TM VII was mutated to alanine, the full-length protein expressed, and its activity characterized. TM VII was sensitive to mutation. Mutations at 13 of 22 residues resulted in severely reduced activity, whereas other mutants exhibited varying degrees of decreases in activity. The impaired activities sometimes resulted from low expression and/or low surface targeting. Three of the alanine scanning mutant proteins displayed increased, and two displayed decreased resistance to the Na(+)/H(+) exchanger isoform 1 inhibitor EMD87580. The structure of a peptide of TM VII was determined by using high resolution NMR in dodecylphosphocholine micelles. TM VII is predominantly alpha-helical, with a break in the helix at the functionally critical residues Gly(261)-Glu(262). The relative positions and orientations of the N- and C-terminal helical segments are seen to vary about this extended segment in the ensemble of NMR structures. Our results show that TM VII is a critical transmembrane segment structured as an interrupted helix, with several residues that are essential to both protein function and sensitivity to inhibition.

Structural and functional characterization of transmembrane segment VII of the Na+/H+ exchanger isoform 1.,Ding J, Rainey JK, Xu C, Sykes BD, Fliegel L J Biol Chem. 2006 Oct 6;281(40):29817-29. Epub 2006 Jul 21. PMID:16861220<ref>PMID:16861220</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2htg" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ding J]]
[[Category: Fliegel L]]
[[Category: Rainey JK]]
[[Category: Sykes BD]]
[[Category: Xu C]]