7e8h: Difference between revisions

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-'''Unreleased structure'''
-The entry 7e8h is ON HOLD  until Paper Publication
+==CryoEM structure of human Kv4.2-DPP6S-KChIP1 complex==
+<StructureSection load='7e8h' size='340' side='right'caption='[[7e8h]], [[Resolution|resolution]] 4.50&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7e8h]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7E8H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7E8H FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.5&#8491;</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=7e8h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7e8h OCA], [https://pdbe.org/7e8h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7e8h RCSB], [https://www.ebi.ac.uk/pdbsum/7e8h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7e8h ProSAT]</span></td></tr>
+</table>
+== Disease ==
+[https://www.uniprot.org/uniprot/DPP6_HUMAN DPP6_HUMAN] Autosomal dominant primary microcephaly;Idiopathic ventricular fibrillation, non Brugada type. The disease is caused by variants affecting the gene represented in this entry. A genetic variation 340 bases upstream from the ATG start site of the DPP6 gene is the cause of familial paroxysmal ventricular fibrillation type 2.  The disease is caused by variants affecting the gene represented in this entry.
+== Function ==
+[https://www.uniprot.org/uniprot/DPP6_HUMAN DPP6_HUMAN] Promotes cell surface expression of the potassium channel KCND2 (PubMed:15454437, PubMed:19441798). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:18364354). Has no dipeptidyl aminopeptidase activity (PubMed:8103397, PubMed:15476821).<ref>PMID:15454437</ref> <ref>PMID:18364354</ref> <ref>PMID:8103397</ref> <ref>PMID:15476821</ref>
+<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.
-Authors:
+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>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7e8h" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dipeptidyl peptidase 3D structures|Dipeptidyl peptidase 3D structures]]
+*[[Potassium channel 3D structures|Potassium channel 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Kise Y]]
+[[Category: Nureki O]]