4i2s: Difference between revisions
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[[ | ==Crystal structure of rabbit ryanodine receptor 1 (residues 1-536) disease mutant I404M== | ||
<StructureSection load='4i2s' size='340' side='right' caption='[[4i2s]], [[Resolution|resolution]] 2.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4i2s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I2S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I2S FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2xoa|2xoa]], [[4i0y|4i0y]], [[4i1e|4i1e]], [[4i37|4i37]], [[4i3n|4i3n]], [[4i6i|4i6i]], [[4i7i|4i7i]], [[4i8m|4i8m]], [[4i96|4i96]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RYR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9986 Oryctolagus cuniculus])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i2s OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4i2s RCSB], [http://www.ebi.ac.uk/pdbsum/4i2s PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Ryanodine receptors are large channels that release Ca(2+) from the endoplasmic and sarcoplasmic reticulum. Hundreds of RyR mutations can cause cardiac and skeletal muscle disorders, yet detailed mechanisms explaining their effects have been lacking. Here we compare pseudo-atomic models and propose that channel opening coincides with widening of a cytoplasmic vestibule formed by the N-terminal region, thus altering an interface targeted by 20 disease mutations. We solve crystal structures of several disease mutants that affect intrasubunit domain-domain interfaces. Mutations affecting intrasubunit ionic pairs alter relative domain orientations, and thus couple to surrounding interfaces. Buried disease mutations cause structural changes that also connect to the intersubunit contact area. These results suggest that the intersubunit contact region between N-terminal domains is a prime target for disease mutations, direct or indirect, and we present a model whereby ryanodine receptors and inositol-1,4,5-trisphosphate receptors are activated by altering domain arrangements in the N-terminal region. | |||
Disease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface.,Kimlicka L, Lau K, Tung CC, Van Petegem F Nat Commun. 2013;4:1506. doi: 10.1038/ncomms2501. PMID:23422674<ref>PMID:23422674</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
== References == | |||
<references/> | |||
== | __TOC__ | ||
</StructureSection> | |||
[[Category: Oryctolagus cuniculus]] | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Kimlicka, L | [[Category: Kimlicka, L]] | ||
[[Category: Petegem, F Van | [[Category: Petegem, F Van]] | ||
[[Category: Calcium channel]] | [[Category: Calcium channel]] | ||
[[Category: Metal transport]] | [[Category: Metal transport]] | ||
[[Category: Sr/er membrane]] | [[Category: Sr/er membrane]] | ||
Revision as of 20:06, 10 December 2014
Crystal structure of rabbit ryanodine receptor 1 (residues 1-536) disease mutant I404MCrystal structure of rabbit ryanodine receptor 1 (residues 1-536) disease mutant I404M
Structural highlights
Publication Abstract from PubMedRyanodine receptors are large channels that release Ca(2+) from the endoplasmic and sarcoplasmic reticulum. Hundreds of RyR mutations can cause cardiac and skeletal muscle disorders, yet detailed mechanisms explaining their effects have been lacking. Here we compare pseudo-atomic models and propose that channel opening coincides with widening of a cytoplasmic vestibule formed by the N-terminal region, thus altering an interface targeted by 20 disease mutations. We solve crystal structures of several disease mutants that affect intrasubunit domain-domain interfaces. Mutations affecting intrasubunit ionic pairs alter relative domain orientations, and thus couple to surrounding interfaces. Buried disease mutations cause structural changes that also connect to the intersubunit contact area. These results suggest that the intersubunit contact region between N-terminal domains is a prime target for disease mutations, direct or indirect, and we present a model whereby ryanodine receptors and inositol-1,4,5-trisphosphate receptors are activated by altering domain arrangements in the N-terminal region. Disease mutations in the ryanodine receptor N-terminal region couple to a mobile intersubunit interface.,Kimlicka L, Lau K, Tung CC, Van Petegem F Nat Commun. 2013;4:1506. doi: 10.1038/ncomms2501. PMID:23422674[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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