2mng: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[2mng]] 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=2MNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MNG FirstGlance]. <br>
<table><tr><td colspan='2'>[[2mng]] 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=2MNG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MNG 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=2mng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mng OCA], [https://pdbe.org/2mng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mng RCSB], [https://www.ebi.ac.uk/pdbsum/2mng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mng ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mng FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mng OCA], [https://pdbe.org/2mng PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mng RCSB], [https://www.ebi.ac.uk/pdbsum/2mng PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mng ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
== Disease ==
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== Function ==
== Function ==
[https://www.uniprot.org/uniprot/HCN4_HUMAN HCN4_HUMAN] Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli.<ref>PMID:10228147</ref> <ref>PMID:10430953</ref>  
[https://www.uniprot.org/uniprot/HCN4_HUMAN HCN4_HUMAN] Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) and in neurons (Ih). Activated by cAMP. May mediate responses to sour stimuli.<ref>PMID:10228147</ref> <ref>PMID:10430953</ref>  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels control neuronal and cardiac electrical rhythmicity. There are four homologous isoforms (HCN1-4) sharing a common multidomain architecture that includes an N-terminal transmembrane tetrameric ion channel followed by a cytoplasmic "C-linker," which connects a more distal cAMP-binding domain (CBD) to the inner pore. Channel opening is primarily stimulated by transmembrane elements that sense membrane hyperpolarization, although cAMP reduces the voltage required for HCN activation by promoting tetramerization of the intracellular C-linker, which in turn relieves auto-inhibition of the inner pore gate. Although binding of cAMP has been proposed to relieve auto-inhibition by affecting the structure of the C-linker and CBD, the nature and extent of these cAMP-dependent changes remain limitedly explored. Here, we used NMR to probe the changes caused by the binding of cAMP and of cCMP, a partial agonist, to the apo-CBD of HCN4. Our data indicate that the CBD exists in a dynamic two-state equilibrium, whose position as gauged by NMR chemical shifts correlates with the V(1/2) voltage measured through electrophysiology. In the absence of cAMP, the most populated CBD state leads to steric clashes with the activated or "tetrameric" C-linker, which becomes energetically unfavored. The steric clashes of the apo tetramer are eliminated either by cAMP binding, which selects for a CBD state devoid of steric clashes with the tetrameric C-linker and facilitates channel opening, or by a transition of apo-HCN to monomers or dimer of dimers, in which the C-linker becomes less structured, and channel opening is not facilitated.
A mechanism for the auto-inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel opening and its relief by cAMP.,Akimoto M, Zhang Z, Boulton S, Selvaratnam R, VanSchouwen B, Gloyd M, Accili EA, Lange OF, Melacini G J Biol Chem. 2014 Aug 8;289(32):22205-20. doi: 10.1074/jbc.M114.572164. Epub 2014, May 30. PMID:24878962<ref>PMID:24878962</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2mng" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
Retrieved from "https://proteopedia.org/2mng"