4msw: Difference between revisions
New page: '''Unreleased structure''' The entry 4msw is ON HOLD Authors: Matulef, K., Valiyaveetil, F.I. Description: Y78 ester mutant of KcsA in high K+ |
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==Y78 ester mutant of KcsA in high K+== | |||
<StructureSection load='4msw' size='340' side='right'caption='[[4msw]], [[Resolution|resolution]] 2.06Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4msw]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MSW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MSW FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DGA:DIACYL+GLYCEROL'>DGA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=TYF:(2S)-2-HYDROXY-3-(4-HYDROXYPHENYL)PROPANOIC+ACID'>TYF</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=4msw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4msw OCA], [https://pdbe.org/4msw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4msw RCSB], [https://www.ebi.ac.uk/pdbsum/4msw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4msw ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/KCSA_STRLI KCSA_STRLI] Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).<ref>PMID:7489706</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
K+ channels distinguish K+ from Na+ in the selectivity filter, which consists of four ion-binding sites (S1-S4, extracellular to intracellular) that are built mainly using the carbonyl oxygens from the protein backbone. In addition to ionic discrimination, the selectivity filter regulates the flow of ions across the membrane in a gating process referred to as C-type inactivation. A characteristic of C-type inactivation is a dependence on the permeant ion, but the mechanism by which permeant ions modulate C-type inactivation is not known. To investigate, we used amide-to-ester substitutions in the protein backbone of the selectivity filter to alter ion binding at specific sites and determined the effects on inactivation. The amide-to-ester substitutions in the protein backbone were introduced using protein semisynthesis or in vivo nonsense suppression approaches. We show that an ester substitution at the S1 site in the KcsA channel does not affect inactivation whereas ester substitutions at the S2 and S3 sites dramatically reduce inactivation. We determined the structure of the KcsA S2 ester mutant and found that the ester substitution eliminates K+ binding at the S2 site. We also show that an ester substitution at the S2 site in the KvAP channel has a similar effect of slowing inactivation. Our results link C-type inactivation to ion occupancy at the S2 site. Furthermore, they suggest that the differences in inactivation of K+ channels in K+ compared with Rb+ are due to different ion occupancies at the S2 site. | |||
Using protein backbone mutagenesis to dissect the link between ion occupancy and C-type inactivation in K+ channels.,Matulef K, Komarov AG, Costantino CA, Valiyaveetil FI Proc Natl Acad Sci U S A. 2013 Oct 15. PMID:24128761<ref>PMID:24128761</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 4msw" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Mus musculus]] | |||
[[Category: Streptomyces lividans]] | |||
[[Category: Matulef K]] | |||
[[Category: Valiyaveetil FI]] | |||
Latest revision as of 13:06, 28 December 2022
Y78 ester mutant of KcsA in high K+Y78 ester mutant of KcsA in high K+
Structural highlights
FunctionKCSA_STRLI Acts as a pH-gated potassium ion channel; changing the cytosolic pH from 7 to 4 opens the channel, although it is not clear if this is the physiological stimulus for channel opening. Monovalent cation preference is K(+) > Rb(+) > NH4(+) >> Na(+) > Li(+).[1] Publication Abstract from PubMedK+ channels distinguish K+ from Na+ in the selectivity filter, which consists of four ion-binding sites (S1-S4, extracellular to intracellular) that are built mainly using the carbonyl oxygens from the protein backbone. In addition to ionic discrimination, the selectivity filter regulates the flow of ions across the membrane in a gating process referred to as C-type inactivation. A characteristic of C-type inactivation is a dependence on the permeant ion, but the mechanism by which permeant ions modulate C-type inactivation is not known. To investigate, we used amide-to-ester substitutions in the protein backbone of the selectivity filter to alter ion binding at specific sites and determined the effects on inactivation. The amide-to-ester substitutions in the protein backbone were introduced using protein semisynthesis or in vivo nonsense suppression approaches. We show that an ester substitution at the S1 site in the KcsA channel does not affect inactivation whereas ester substitutions at the S2 and S3 sites dramatically reduce inactivation. We determined the structure of the KcsA S2 ester mutant and found that the ester substitution eliminates K+ binding at the S2 site. We also show that an ester substitution at the S2 site in the KvAP channel has a similar effect of slowing inactivation. Our results link C-type inactivation to ion occupancy at the S2 site. Furthermore, they suggest that the differences in inactivation of K+ channels in K+ compared with Rb+ are due to different ion occupancies at the S2 site. Using protein backbone mutagenesis to dissect the link between ion occupancy and C-type inactivation in K+ channels.,Matulef K, Komarov AG, Costantino CA, Valiyaveetil FI Proc Natl Acad Sci U S A. 2013 Oct 15. PMID:24128761[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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