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==Structure of the (SR)Ca2+-ATPase mutant E340A in the Ca2-E1-CaAMPPCP form== | ==Structure of the (SR)Ca2+-ATPase mutant E340A in the Ca2-E1-CaAMPPCP form== | ||
<StructureSection load='6rb2' size='340' side='right'caption='[[6rb2]]' scene=''> | <StructureSection load='6rb2' size='340' side='right'caption='[[6rb2]], [[Resolution|resolution]] 3.20Å' 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=6RB2 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[6rb2]] is a 1 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=6RB2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RB2 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2000113Å</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=K:POTASSIUM+ION'>K</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=6rb2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rb2 OCA], [https://pdbe.org/6rb2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rb2 RCSB], [https://www.ebi.ac.uk/pdbsum/6rb2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rb2 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/AT2A1_RABIT AT2A1_RABIT] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction (By similarity). | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) is a P-type ATPase that transports Ca(2+) from the cytosol into the sarco(endo)plasmic reticulum (SR/ER) lumen, driven by ATP. This primary transport activity depends on tight coupling between movements of the transmembrane helices forming the two Ca(2+)-binding sites and the cytosolic headpiece mediating ATP hydrolysis. We have addressed the molecular basis for this intramolecular communication by analyzing the structure and functional properties of the SERCA mutant E340A. The mutated Glu340 residue is strictly conserved among the P-type ATPase family of membrane transporters and is located at a seemingly strategic position at the interface between the phosphorylation domain and the cytosolic ends of 5 of SERCA's 10 transmembrane helices. The mutant displays a marked slowing of the Ca(2+)-binding kinetics, and its crystal structure in the presence of Ca(2+) and ATP analog reveals a rotated headpiece, altered connectivity between the cytosolic domains, and an altered hydrogen bonding pattern around residue 340. Supported by molecular dynamics simulations, we conclude that the E340A mutation causes a stabilization of the Ca(2+) sites in a more occluded state, hence displaying slowed dynamics. This finding underpins a crucial role of Glu340 in interdomain communication between the headpiece and the Ca(2+)-binding transmembrane region. | |||
The SERCA residue Glu340 mediates interdomain communication that guides Ca(2+) transport.,Geurts MMG, Clausen JD, Arnou B, Montigny C, Lenoir G, Corey RA, Jaxel C, Moller JV, Nissen P, Andersen JP, le Maire M, Bublitz M Proc Natl Acad Sci U S A. 2020 Nov 23. pii: 2014896117. doi:, 10.1073/pnas.2014896117. PMID:33229570<ref>PMID:33229570</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6rb2" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[ATPase 3D structures|ATPase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Oryctolagus cuniculus]] | |||
[[Category: Andersen JP]] | [[Category: Andersen JP]] | ||
[[Category: Arnou B]] | [[Category: Arnou B]] | ||
Latest revision as of 15:18, 24 January 2024
Structure of the (SR)Ca2+-ATPase mutant E340A in the Ca2-E1-CaAMPPCP formStructure of the (SR)Ca2+-ATPase mutant E340A in the Ca2-E1-CaAMPPCP form
Structural highlights
FunctionAT2A1_RABIT This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction (By similarity). Publication Abstract from PubMedThe sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) is a P-type ATPase that transports Ca(2+) from the cytosol into the sarco(endo)plasmic reticulum (SR/ER) lumen, driven by ATP. This primary transport activity depends on tight coupling between movements of the transmembrane helices forming the two Ca(2+)-binding sites and the cytosolic headpiece mediating ATP hydrolysis. We have addressed the molecular basis for this intramolecular communication by analyzing the structure and functional properties of the SERCA mutant E340A. The mutated Glu340 residue is strictly conserved among the P-type ATPase family of membrane transporters and is located at a seemingly strategic position at the interface between the phosphorylation domain and the cytosolic ends of 5 of SERCA's 10 transmembrane helices. The mutant displays a marked slowing of the Ca(2+)-binding kinetics, and its crystal structure in the presence of Ca(2+) and ATP analog reveals a rotated headpiece, altered connectivity between the cytosolic domains, and an altered hydrogen bonding pattern around residue 340. Supported by molecular dynamics simulations, we conclude that the E340A mutation causes a stabilization of the Ca(2+) sites in a more occluded state, hence displaying slowed dynamics. This finding underpins a crucial role of Glu340 in interdomain communication between the headpiece and the Ca(2+)-binding transmembrane region. The SERCA residue Glu340 mediates interdomain communication that guides Ca(2+) transport.,Geurts MMG, Clausen JD, Arnou B, Montigny C, Lenoir G, Corey RA, Jaxel C, Moller JV, Nissen P, Andersen JP, le Maire M, Bublitz M Proc Natl Acad Sci U S A. 2020 Nov 23. pii: 2014896117. doi:, 10.1073/pnas.2014896117. PMID:33229570[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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