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==CryoEM structure of the human Kv4.2-KChIP1 complex, transmembrane region== | ==CryoEM structure of the human Kv4.2-KChIP1 complex, transmembrane region== | ||
<StructureSection load='7e7z' size='340' side='right'caption='[[7e7z]]' scene=''> | <StructureSection load='7e7z' size='340' side='right'caption='[[7e7z]], [[Resolution|resolution]] 3.20Å' 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=7E7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E7Z FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E7Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E7Z 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=7e7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e7z OCA], [https://pdbe.org/7e7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e7z RCSB], [https://www.ebi.ac.uk/pdbsum/7e7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e7z ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.2Å</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=7e7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e7z OCA], [https://pdbe.org/7e7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e7z RCSB], [https://www.ebi.ac.uk/pdbsum/7e7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e7z ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Modulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart(1,2). Native Kv4 tetrameric channels form macromolecular ternary complexes with two auxiliary beta-subunits-intracellular Kv channel-interacting proteins (KChIPs) and transmembrane dipeptidyl peptidase-related proteins (DPPs)-to evoke rapidly activating and inactivating A-type currents, which prevent the backpropagation of action potentials(1-5). However, the modulatory mechanisms of Kv4 channel complexes remain largely unknown. Here we report cryo-electron microscopy structures of the Kv4.2-DPP6S-KChIP1 dodecamer complex, the Kv4.2-KChIP1 and Kv4.2-DPP6S octamer complexes, and Kv4.2 alone. The structure of the Kv4.2-KChIP1 complex reveals that the intracellular N terminus of Kv4.2 interacts with its C terminus that extends from the S6 gating helix of the neighbouring Kv4.2 subunit. KChIP1 captures both the N and the C terminus of Kv4.2. In consequence, KChIP1 would prevent N-type inactivation and stabilize the S6 conformation to modulate gating of the S6 helices within the tetramer. By contrast, unlike the reported auxiliary subunits of voltage-gated channel complexes, DPP6S interacts with the S1 and S2 helices of the Kv4.2 voltage-sensing domain, which suggests that DPP6S stabilizes the conformation of the S1-S2 helices. DPP6S may therefore accelerate the voltage-dependent movement of the S4 helices. KChIP1 and DPP6S do not directly interact with each other in the Kv4.2-KChIP1-DPP6S ternary complex. Thus, our data suggest that two distinct modes of modulation contribute in an additive manner to evoke A-type currents from the native Kv4 macromolecular complex. | |||
Structural basis of gating modulation of Kv4 channel complexes.,Kise Y, Kasuya G, Okamoto HH, Yamanouchi D, Kobayashi K, Kusakizako T, Nishizawa T, Nakajo K, Nureki O Nature. 2021 Sep 22. pii: 10.1038/s41586-021-03935-z. doi:, 10.1038/s41586-021-03935-z. PMID:34552243<ref>PMID:34552243</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7e7z" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 08:43, 5 June 2024
CryoEM structure of the human Kv4.2-KChIP1 complex, transmembrane regionCryoEM structure of the human Kv4.2-KChIP1 complex, transmembrane region
Structural highlights
Publication Abstract from PubMedModulation of voltage-gated potassium (Kv) channels by auxiliary subunits is central to the physiological function of channels in the brain and heart(1,2). Native Kv4 tetrameric channels form macromolecular ternary complexes with two auxiliary beta-subunits-intracellular Kv channel-interacting proteins (KChIPs) and transmembrane dipeptidyl peptidase-related proteins (DPPs)-to evoke rapidly activating and inactivating A-type currents, which prevent the backpropagation of action potentials(1-5). However, the modulatory mechanisms of Kv4 channel complexes remain largely unknown. Here we report cryo-electron microscopy structures of the Kv4.2-DPP6S-KChIP1 dodecamer complex, the Kv4.2-KChIP1 and Kv4.2-DPP6S octamer complexes, and Kv4.2 alone. The structure of the Kv4.2-KChIP1 complex reveals that the intracellular N terminus of Kv4.2 interacts with its C terminus that extends from the S6 gating helix of the neighbouring Kv4.2 subunit. KChIP1 captures both the N and the C terminus of Kv4.2. In consequence, KChIP1 would prevent N-type inactivation and stabilize the S6 conformation to modulate gating of the S6 helices within the tetramer. By contrast, unlike the reported auxiliary subunits of voltage-gated channel complexes, DPP6S interacts with the S1 and S2 helices of the Kv4.2 voltage-sensing domain, which suggests that DPP6S stabilizes the conformation of the S1-S2 helices. DPP6S may therefore accelerate the voltage-dependent movement of the S4 helices. KChIP1 and DPP6S do not directly interact with each other in the Kv4.2-KChIP1-DPP6S ternary complex. Thus, our data suggest that two distinct modes of modulation contribute in an additive manner to evoke A-type currents from the native Kv4 macromolecular complex. Structural basis of gating modulation of Kv4 channel complexes.,Kise Y, Kasuya G, Okamoto HH, Yamanouchi D, Kobayashi K, Kusakizako T, Nishizawa T, Nakajo K, Nureki O Nature. 2021 Sep 22. pii: 10.1038/s41586-021-03935-z. doi:, 10.1038/s41586-021-03935-z. PMID:34552243[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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