7tdh: Difference between revisions
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==Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in open conformation== | ==Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in open conformation== | ||
<StructureSection load='7tdh' size='340' side='right'caption='[[7tdh]]' scene=''> | <StructureSection load='7tdh' size='340' side='right'caption='[[7tdh]], [[Resolution|resolution]] 4.00Å' 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=7TDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDH FirstGlance]. <br> | <table><tr><td colspan='2'>[[7tdh]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Oryctolagus_cuniculus Oryctolagus cuniculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TDH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TDH 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=7tdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tdh OCA], [https://pdbe.org/7tdh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tdh RCSB], [https://www.ebi.ac.uk/pdbsum/7tdh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tdh ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACP:PHOSPHOMETHYLPHOSPHONIC+ACID+ADENYLATE+ESTER'>ACP</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</scene></td></tr> | |||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7tdg|7tdg]], [[7tdj|7tdj]], [[7tdi|7tdi]], [[7tdk|7tdk]], [[7k0t|7k0t]]</div></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=7tdh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tdh OCA], [https://pdbe.org/7tdh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tdh RCSB], [https://www.ebi.ac.uk/pdbsum/7tdh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tdh ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[https://www.uniprot.org/uniprot/RYR1_RABIT RYR1_RABIT]] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).<ref>PMID:10388749</ref> <ref>PMID:22036948</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Activation of the intracellular Ca(2+) channel ryanodine receptor (RyR) triggers a cytosolic Ca(2+) surge, while elevated cytosolic Ca(2+) inhibits the channel in a negative feedback mechanism. Cryo-EM of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca(2+) conditions revealed an open and a closed-inactivated conformation. Ca(2+) binding to the high affinity site engages the central and C-terminal domains into a block, which pries the S6 four-helix bundle open. Further rotation of this block pushes S6 toward the central axis, closing (inactivating) the channel. Main characteristics of the Ca(2+)-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly-knit subunit interface contributed by a fully occupied Ca(2+) activation site, two inter-subunit resolved lipids, and two salt bridges between the EF hand domain and the S2-S3 loop validated by disease-causing mutations. The structural insight illustrates the prior Ca(2+) activation prerequisite for Ca(2+) inactivation and provides for seamless transition from inactivated to closed conformations. | |||
Ca(2+)-inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM.,Nayak AR, Samso M Elife. 2022 Mar 8;11. pii: 75568. doi: 10.7554/eLife.75568. PMID:35257661<ref>PMID:35257661</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7tdh" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Nayak | [[Category: Oryctolagus cuniculus]] | ||
[[Category: Samso M]] | [[Category: Nayak, A R]] | ||
[[Category: Samso, M]] | |||
[[Category: Ca2+]] | |||
[[Category: Excitation-contraction coupling]] | |||
[[Category: Inactivation]] | |||
[[Category: Intracellular calcium channel]] | |||
[[Category: Ryanodine receptor]] | |||
[[Category: Ryr1]] | |||
[[Category: Transport protein]] | |||
Revision as of 10:24, 16 March 2022
Rabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in open conformationRabbit RyR1 with AMP-PCP and high Ca2+ embedded in nanodisc in open conformation
Structural highlights
Function[RYR1_RABIT] Calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytoplasm and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules. Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm. Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).[1] [2] Publication Abstract from PubMedActivation of the intracellular Ca(2+) channel ryanodine receptor (RyR) triggers a cytosolic Ca(2+) surge, while elevated cytosolic Ca(2+) inhibits the channel in a negative feedback mechanism. Cryo-EM of rabbit RyR1 embedded in nanodiscs under partially inactivating Ca(2+) conditions revealed an open and a closed-inactivated conformation. Ca(2+) binding to the high affinity site engages the central and C-terminal domains into a block, which pries the S6 four-helix bundle open. Further rotation of this block pushes S6 toward the central axis, closing (inactivating) the channel. Main characteristics of the Ca(2+)-inactivated conformation are downward conformation of the cytoplasmic assembly and tightly-knit subunit interface contributed by a fully occupied Ca(2+) activation site, two inter-subunit resolved lipids, and two salt bridges between the EF hand domain and the S2-S3 loop validated by disease-causing mutations. The structural insight illustrates the prior Ca(2+) activation prerequisite for Ca(2+) inactivation and provides for seamless transition from inactivated to closed conformations. Ca(2+)-inactivation of the mammalian ryanodine receptor type 1 in a lipidic environment revealed by cryo-EM.,Nayak AR, Samso M Elife. 2022 Mar 8;11. pii: 75568. doi: 10.7554/eLife.75568. PMID:35257661[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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