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| | ==Structure of magnesium-loaded ALG-2== | | ==Structure of magnesium-loaded ALG-2== |
| - | <StructureSection load='5jjg' size='340' side='right' caption='[[5jjg]], [[Resolution|resolution]] 1.72Å' scene=''> | + | <StructureSection load='5jjg' size='340' side='right'caption='[[5jjg]], [[Resolution|resolution]] 1.72Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5jjg]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JJG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5JJG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5jjg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5JJG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5JJG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.72Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pdcd6, Alg2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5jjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jjg OCA], [http://pdbe.org/5jjg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5jjg RCSB], [http://www.ebi.ac.uk/pdbsum/5jjg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5jjg 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=5jjg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5jjg OCA], [https://pdbe.org/5jjg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5jjg RCSB], [https://www.ebi.ac.uk/pdbsum/5jjg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5jjg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PDCD6_MOUSE PDCD6_MOUSE]] Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101 (By similarity). May mediate Ca(2+)-regulated signals along the death pathway. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (By similarity). | + | [https://www.uniprot.org/uniprot/PDCD6_MOUSE PDCD6_MOUSE] Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101 (By similarity). May mediate Ca(2+)-regulated signals along the death pathway. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (By similarity). |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Tanner, J J]] | + | [[Category: Mus musculus]] |
| - | [[Category: Alg-2]] | + | [[Category: Tanner JJ]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Apoptosis-linked gene 2]]
| + | |
| - | [[Category: Calcium binding protein]]
| + | |
| - | [[Category: Penta-ef-hand protein]]
| + | |
| Structural highlights
Function
PDCD6_MOUSE Calcium-binding protein required for T-cell receptor-, Fas-, and glucocorticoid-induced cell death. Calcium-dependent adapter necessary for the association between PDCD6IP and TSG101 (By similarity). May mediate Ca(2+)-regulated signals along the death pathway. Interaction with DAPK1 can accelerate apoptotic cell death by increasing caspase-3 activity (By similarity).
Publication Abstract from PubMed
The penta-EF-hand (PEF) protein ALG-2 (apoptosis-linked gene 2) has been implicated in several important physiological processes, including endoplasmic reticulum-Golgi vesicular transport and endosomal biogenesis/transport. ALG-2 was recently shown to harbor a metal ion-binding site with a high affinity for Mg2+ and a low affinity for Ca2+. We herein present the X-ray structure of Mg2+-bound ALG-2des23wt. Although the Calpha trace is nearly indistinguishable from that of the Ca2+-free protein, the orientation of the C-terminal helix differs in the two structures. Consistent with that observation, replacement of the +x ligand in EF5, D169, with alanine eliminates high-affinity Mg2+ binding. It also eliminates the low-affinity Ca2+ site and lowers the affinity of the remaining Ca2+-binding sites, EF3 and EF1. The coordination environment in EF5 approaches ideal Mg2+ octahedral geometry. The ligand array, consisting of three carboxylates (+x, +y, +z), a backbone carbonyl (-y), and two water molecules (-x, -z), may offer a recipe for a high-affinity, high-selectivity Mg2+-binding site. Sequence data for other PEF proteins indicate that select calpain large subunits, notably CAPN1 and CAPN8, may also possess a high-affinity Mg2+-binding site. In Mg2+-bound ALG-2, the carbonyl of F188 and the C-terminal carboxylate of V191 interact with the epsilon-ammonium group of K137 in the opposing subunit, suggesting that Mg2+ binding could have an impact on dimerization. Interestingly, EF1 and EF3 are also occupied in the crystal, despite having modest affinity for Mg2+. The results of a calorimetry-based analysis indicate that their Mg2+ binding constants are 2 orders of magnitude lower than that determined for EF5.
EF5 Is the High-Affinity Mg2+ Site in ALG-2.,Tanner JJ, Frey BB, Pemberton T, Henzl MT Biochemistry. 2016 Aug 31. PMID:27541325[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tanner JJ, Frey BB, Pemberton T, Henzl MT. EF5 Is the High-Affinity Mg2+ Site in ALG-2. Biochemistry. 2016 Aug 31. PMID:27541325 doi:http://dx.doi.org/10.1021/acs.biochem.6b00596
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