7mk6: Difference between revisions
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==== | ==KcsA open gate E71V mutant with sodium== | ||
<StructureSection load='7mk6' size='340' side='right'caption='[[7mk6]]' scene=''> | <StructureSection load='7mk6' size='340' side='right'caption='[[7mk6]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | <table><tr><td colspan='2'>[[7mk6]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_lividans Streptomyces lividans] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7MK6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7MK6 FirstGlance]. <br> | ||
</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=7mk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mk6 OCA], [https://pdbe.org/7mk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mk6 RCSB], [https://www.ebi.ac.uk/pdbsum/7mk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mk6 ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</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=7mk6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7mk6 OCA], [https://pdbe.org/7mk6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7mk6 RCSB], [https://www.ebi.ac.uk/pdbsum/7mk6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7mk6 ProSAT]</span></td></tr> | |||
</table> | </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 == | |||
C-type inactivation is of great physiological importance in voltage-activated K(+) channels (Kv), but its structural basis remains unresolved. Knowledge about C-type inactivation has been largely deduced from the bacterial K(+) channel KcsA, whose selectivity filter constricts under inactivating conditions. However, the filter is highly sensitive to its molecular environment, which is different in Kv channels than in KcsA. In particular, a glutamic acid residue at position 71 along the pore helix in KcsA is substituted by a valine conserved in most Kv channels, suggesting that this side chain is a molecular determinant of function. Here, a combination of X-ray crystallography, solid-state NMR and MD simulations of the E71V KcsA mutant is undertaken to explore inactivation in this Kv-like construct. X-ray and ssNMR data show that the filter of the Kv-like mutant does not constrict under inactivating conditions. Rather, the filter adopts a conformation that is slightly narrowed and rigidified. On the other hand, MD simulations indicate that the constricted conformation can nonetheless be stably established in the mutant channel. Together, these findings suggest that the Kv-like KcsA mutant may be associated with different modes of C-type inactivation, showing that distinct filter environments entail distinct C-type inactivation mechanisms. | |||
A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V.,Rohaim A, Vermeulen BJA, Li J, Kummerer F, Napoli F, Blachowicz L, Medeiros-Silva J, Roux B, Weingarth M Nat Commun. 2022 Mar 23;13(1):1574. doi: 10.1038/s41467-022-28866-9. PMID:35322021<ref>PMID:35322021</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7mk6" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Streptomyces lividans]] | ||
[[Category: Synthetic construct]] | |||
[[Category: Li J]] | |||
[[Category: Rohaim A]] | |||
[[Category: Roux B]] | |||
[[Category: Weingarth M]] | |||
Latest revision as of 19:13, 18 October 2023
KcsA open gate E71V mutant with sodiumKcsA open gate E71V mutant with sodium
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 PubMedC-type inactivation is of great physiological importance in voltage-activated K(+) channels (Kv), but its structural basis remains unresolved. Knowledge about C-type inactivation has been largely deduced from the bacterial K(+) channel KcsA, whose selectivity filter constricts under inactivating conditions. However, the filter is highly sensitive to its molecular environment, which is different in Kv channels than in KcsA. In particular, a glutamic acid residue at position 71 along the pore helix in KcsA is substituted by a valine conserved in most Kv channels, suggesting that this side chain is a molecular determinant of function. Here, a combination of X-ray crystallography, solid-state NMR and MD simulations of the E71V KcsA mutant is undertaken to explore inactivation in this Kv-like construct. X-ray and ssNMR data show that the filter of the Kv-like mutant does not constrict under inactivating conditions. Rather, the filter adopts a conformation that is slightly narrowed and rigidified. On the other hand, MD simulations indicate that the constricted conformation can nonetheless be stably established in the mutant channel. Together, these findings suggest that the Kv-like KcsA mutant may be associated with different modes of C-type inactivation, showing that distinct filter environments entail distinct C-type inactivation mechanisms. A distinct mechanism of C-type inactivation in the Kv-like KcsA mutant E71V.,Rohaim A, Vermeulen BJA, Li J, Kummerer F, Napoli F, Blachowicz L, Medeiros-Silva J, Roux B, Weingarth M Nat Commun. 2022 Mar 23;13(1):1574. doi: 10.1038/s41467-022-28866-9. PMID:35322021[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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