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4ehq

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Revision as of 02:49, 11 December 2016

Crystal 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 Buffalo rat. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	Calm1, Calm, Cam, Cam1, Calm2, Cam2, Camb, Calm3, Cam3, Camc (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CRCM1_HUMAN] Combined immunodeficiency due to ORAI1 deficiency. The disease is caused by mutations affecting the gene represented in this entry.

Function

[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.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Soboloff J, Spassova MA, Tang XD, Hewavitharana T, Xu W, Gill DL. Orai1 and STIM reconstitute store-operated calcium channel function. J Biol Chem. 2006 Jul 28;281(30):20661-5. Epub 2006 Jun 9. PMID:16766533 doi:10.1074/jbc.C600126200
↑ Mercer JC, Dehaven WI, Smyth JT, Wedel B, Boyles RR, Bird GS, Putney JW Jr. Large store-operated calcium selective currents due to co-expression of Orai1 or Orai2 with the intracellular calcium sensor, Stim1. J Biol Chem. 2006 Aug 25;281(34):24979-90. Epub 2006 Jun 28. PMID:16807233 doi:M604589200
↑ Peinelt C, Vig M, Koomoa DL, Beck A, Nadler MJ, Koblan-Huberson M, Lis A, Fleig A, Penner R, Kinet JP. Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat Cell Biol. 2006 Jul;8(7):771-3. Epub 2006 May 30. PMID:16733527 doi:ncb1435
↑ Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 2006 May 26;312(5777):1220-3. Epub 2006 Apr 27. PMID:16645049 doi:http://dx.doi.org/10.1126/science.1127883
↑ Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A. A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature. 2006 May 11;441(7090):179-85. Epub 2006 Apr 2. PMID:16582901 doi:http://dx.doi.org/nature04702
↑ Liu Y, Zheng X, Mueller GA, Sobhany M, Derose EF, Zhang Y, London RE, Birnbaumer L. Crystal Structure of Calmodulin Binding Domain of Orai1 in Complex with Ca2+/Calmodulin Displays a Unique Binding Mode. J Biol Chem. 2012 Oct 29. PMID:23109337 doi:http://dx.doi.org/10.1074/jbc.M112.380964

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ehq"

@@ Line 1: / Line 1: @@
 ==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=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ehq]] is a 2 chain structure with sequence from [http://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 [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 [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>
 </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>
-<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 Rattus norvegicus])</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='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://www.rcsb.org/pdb/explore.do?structureId=4ehq RCSB], [http://www.ebi.ac.uk/pdbsum/4ehq PDBsum]</span></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>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 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==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Rattus norvegicus]]
+[[Category: Buffalo rat]]
 [[Category: Birnbaumer, L]]
 [[Category: DeRose, E F]]

4ehq

From Proteopedia

Revision as of 02:49, 11 December 2016

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

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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