View source for 3u10


==Tetramerization dynamics of the C-terminus underlies isoform-specific cAMP-gating in HCN channels==
<StructureSection load='3u10' size='340' side='right'caption='[[3u10]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3u10]] is a 1 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=3U10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U10 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMP:ADENOSINE-3,5-CYCLIC-MONOPHOSPHATE'>CMP</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=3u10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u10 OCA], [https://pdbe.org/3u10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u10 RCSB], [https://www.ebi.ac.uk/pdbsum/3u10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u10 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HCN2_HUMAN HCN2_HUMAN] Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).
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== Publication Abstract from PubMed ==
HCN channels are dually activated by hyperpolarization and binding of cAMP to their cyclic nucleotide binding domain (CNBD). HCN isoforms respond differently to cAMP: binding of cAMP shifts activation of HCN2 and HCN4 by 17 mV, but that of HCN1 by only 2-4 mV. To explain the peculiarity of HCN1 we solved the crystal structures and performed a biochemical-biophysical characterization of the C-terminal domain (C linker + CNBD) of the three isoforms. Our main finding is that tetramerization of the C-terminal domain of HCN1 occurs at basal cAMP concentrations while those of HCN2 and HCN4 require cAMP saturating levels. Therefore, HCN1 responds less markedly than HCN2 and HCN4 to cAMP increase because its CNBD is already partly tetrameric. This is confirmed by voltage clamp experiments showing that the right-shifted position of V1/2 in HCN1 is correlated with its propensity to tetramerize in vitro. These data underscore that ligand-induced CNBD tetramerization removes tonic inhibition from the pore of HCN channels.

Tetramerization dynamics of the C-terminal domain underlies isoform-specific cAMP-gating in Hyperpolarization-activated Cyclic Nucleotide gated channels.,Lolicato M, Nardini M, Gazzarrini S, Moeller S, Bertinetti D, Herberg FW, Bolognesi M, Martin H, Fasolini M, Bertrand JA, Arrigoni C, Thiel G, Moroni A J Biol Chem. 2011 Oct 17. PMID:22006928<ref>PMID:22006928</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 3u10" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arrigoni C]]
[[Category: Bertinetti D]]
[[Category: Bertrand JA]]
[[Category: Bolognesi M]]
[[Category: Fasolini M]]
[[Category: Gazzarrini S]]
[[Category: Herberg FW]]
[[Category: Lolicato M]]
[[Category: Martin H]]
[[Category: Moller S]]
[[Category: Moroni A]]
[[Category: Nardini M]]
[[Category: Thiel G]]