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==Crystal Structure of Calmodulin Binding Domain of Orai1 in Complex with Ca2+/Calmodulin Displays a Unique Binding Mode==
==Crystal Structure of Calmodulin Binding Domain of Orai1 in Complex with Ca2+/Calmodulin Displays a Unique Binding Mode==
<StructureSection load='4ehq' size='340' side='right' caption='[[4ehq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
<StructureSection load='4ehq' size='340' side='right'caption='[[4ehq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4ehq]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EHQ FirstGlance]. <br>
<table><tr><td colspan='2'>[[4ehq]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EHQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EHQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9005&#8491;</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Calm1, Calm, Cam, Cam1, Calm2, Cam2, Camb, Calm3, Cam3, Camc ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GBL:GAMMA-BUTYROLACTONE'>GBL</scene></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=4ehq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehq OCA], [http://pdbe.org/4ehq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ehq RCSB], [http://www.ebi.ac.uk/pdbsum/4ehq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehq ProSAT]</span></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=4ehq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ehq OCA], [https://pdbe.org/4ehq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ehq RCSB], [https://www.ebi.ac.uk/pdbsum/4ehq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ehq ProSAT]</span></td></tr>
</table>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/CRCM1_HUMAN CRCM1_HUMAN]] Combined immunodeficiency due to ORAI1 deficiency. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/CRCM1_HUMAN CRCM1_HUMAN]] Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores and channel activation by the Ca(2+) sensor, STIM1. CRAC channels are the main pathway for Ca(2+) influx in T-cells and promote the immune response to pathogens by activating the transcription factor NFAT.<ref>PMID:16766533</ref> <ref>PMID:16807233</ref> <ref>PMID:16733527</ref> <ref>PMID:16645049</ref> <ref>PMID:16582901</ref> 
[https://www.uniprot.org/uniprot/CALM1_RAT CALM1_RAT] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.[UniProtKB:P62158]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Orai1 is a plasma membrane protein which in its tetrameric form is responsible for calcium influx from the extracellular environment into cytosol in response to interaction with the Ca2+-depletion sensor STIM1. This is followed by a fast Ca2+/calmodulin (CaM)-dependent inhibition, resulting from CaM binding to an Orai1 region called calmodulin binding domain (CMBD). The interaction between Orai1 and CaM at the atomic level remains unknown. Here, we report the crystal structure of a CaM/Orai1-CMBD complex showing one CMBD bound to the C-terminal lobe of CaM, differing from other CaM/target protein complexes, in which both N- and C-terminal lobes of CaM (CaM-N and CaM-C) are involved in target binding. Orai1-CMBD binds CaM-C mainly through hydrophobic interactions, involving primarily residue W76 of Orai1-CMBD which interacts with the hydrophobic pocket of CaM-C. However, NMR data, isothermal titration calorimetry data, and pull-down assays indicated that CaM-N and CaM-C both can bind Orai1-CMBD, with CaM-N having ~4 times weaker affinity than CaM-C. Pull-down assays of a Orai1-CMBD(W76E) mutant, gel filtration chromatography data and NOE signals indicated that CaM-N and CaM-C can each bind one Orai1-CMBD. Thus our studies support an unusual, extended 1:2 binding mode of CaM to Orai1-CMBDs, and quantify the affinity of Orai1 for CaM. We propose a two-step mechanism for CaM-dependent Orai1 inactivation initiated by binding of the C-lobe of CaM to the CMBD of one Orai1 followed by the binding of the N-lobe of CaM to the CMBD of a neighboring Orai1.
 
Crystal Structure of Calmodulin Binding Domain of Orai1 in Complex with Ca2+/Calmodulin Displays a Unique Binding Mode.,Liu Y, Zheng X, Mueller GA, Sobhany M, Derose EF, Zhang Y, London RE, Birnbaumer L J Biol Chem. 2012 Oct 29. PMID:23109337<ref>PMID:23109337</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4ehq" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Calmodulin|Calmodulin]]
*[[Calmodulin 3D structures|Calmodulin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Buffalo rat]]
[[Category: Homo sapiens]]
[[Category: Birnbaumer, L]]
[[Category: Large Structures]]
[[Category: DeRose, E F]]
[[Category: Rattus norvegicus]]
[[Category: Liu, Y]]
[[Category: Birnbaumer L]]
[[Category: London, R E]]
[[Category: DeRose EF]]
[[Category: Mueller, G A]]
[[Category: Liu Y]]
[[Category: Sobhany, M]]
[[Category: London RE]]
[[Category: Zhang, Y]]
[[Category: Mueller GA]]
[[Category: Zheng, X]]
[[Category: Sobhany M]]
[[Category: Calcium binding]]
[[Category: Zhang Y]]
[[Category: Calcium dependent inactivation]]
[[Category: Zheng X]]
[[Category: Calcium-dependent inactivation]]
[[Category: Calmodulin]]
[[Category: Calmodulin binding domain of orai1]]
[[Category: Cytosol]]
[[Category: Ef hand]]
[[Category: None]]
[[Category: Orai1]]
[[Category: Protein binding]]

Latest revision as of 18:01, 14 March 2024

Crystal Structure of Calmodulin Binding Domain of Orai1 in Complex with Ca2+/Calmodulin Displays a Unique Binding ModeCrystal Structure of Calmodulin Binding Domain of Orai1 in Complex with Ca2+/Calmodulin Displays a Unique Binding Mode

Structural highlights

4ehq is a 2 chain structure with sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9005Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CALM1_RAT Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2.[UniProtKB:P62158]

See Also

4ehq, resolution 1.90Å

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