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New page: left|200px<br /><applet load="1hqv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1hqv, resolution 2.3Å" /> '''STRUCTURE OF APOPTOSI...
 
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[[Image:1hqv.jpg|left|200px]]<br /><applet load="1hqv" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1hqv, resolution 2.3&Aring;" />
'''STRUCTURE OF APOPTOSIS-LINKED PROTEIN ALG-2'''<br />


==Overview==
==STRUCTURE OF APOPTOSIS-LINKED PROTEIN ALG-2==
BACKGROUND: The Ca2+ binding apoptosis-linked gene-2 (ALG-2) protein acts, as a proapoptotic factor in a variety of cell lines and is required either, downstream or independently of caspases for apoptosis to occur. ALG-2, belongs to the penta-EF-hand (PEF) protein family and has two, high-affinity and one low-affinity Ca2+ binding sites. Like other PEF, proteins, its N terminus contains a Gly/Pro-rich segment. Ca2+ binding is, required for the interaction with the target protein, ALG-2 interacting, protein 1 (AIP1). RESULTS: We present the 2.3 A resolution crystal, structure of Ca2+-Ioaded des1-20ALG-2 (aa 21-191), which was obtained by, limited proteolysis of recombinant ALG-2 with elastase. The molecule, contains eight alpha helices that fold into five EF-hands, and, similar to, other members of this protein family, the molecule forms dimers. Ca2+ ions, bind to EF1, EF3, and, surprisingly, to EF5. In the related proteins, calpain and grancalcin, the EF5 does not bind Ca2+ and is thought to, primarily facilitate dimerization. Most importantly, the conformation of, des1-20ALG-2 is significantly different from that of calpain and, grancalcin. This difference can be described as a rigid body rotation of, EF1-2 relative to EF4-5 and the dimer interface, with a hinge within the, EF3 loop. An electron density, which is interpreted as a hydrophobic, Gly/Pro-rich decapeptide that is possibly derived from the cleaved N, terminus, was found in a hydrophobic cleft between these two halves of the, molecule. CONCLUSIONS: A different relative orientation of the N- and, C-terminal halves of des1-20ALG-2 in the presence of Ca2+ and the peptide, as compared to other Ca2+loaded PEF proteins changes substantially the, shape of the molecule, exposing a hydrophobic patch on the surface for, peptide binding and a large cleft near the dimer interface. We postulate, that the binding of a Gly/ Pro-rich peptide in the presence of Ca2+, induces a conformational rearrangement in ALG-2, and that this mechanism, is common to other PEF proteins.
<StructureSection load='1hqv' size='340' side='right'caption='[[1hqv]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1hqv]] 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=1HQV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HQV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</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></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=1hqv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hqv OCA], [https://pdbe.org/1hqv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hqv RCSB], [https://www.ebi.ac.uk/pdbsum/1hqv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hqv ProSAT]</span></td></tr>
</table>
== Function ==
[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).
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hq/1hqv_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1hqv ConSurf].
<div style="clear:both"></div>


==About this Structure==
==See Also==
1HQV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CA as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1HQV OCA].
*[[Cell death protein 3D structures|Cell death protein 3D structures]]
 
__TOC__
==Reference==
</StructureSection>
Structure of apoptosis-linked protein ALG-2: insights into Ca2+-induced changes in penta-EF-hand proteins., Jia J, Tarabykina S, Hansen C, Berchtold M, Cygler M, Structure. 2001 Apr 4;9(4):267-75. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11525164 11525164]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Berchtold M]]
[[Category: Berchtold, M.]]
[[Category: Cygler M]]
[[Category: Cygler, M.]]
[[Category: Hansen C]]
[[Category: Hansen, C.]]
[[Category: Jia J]]
[[Category: Jia, J.]]
[[Category: Tarabykina S]]
[[Category: Tarabykina, S.]]
[[Category: CA]]
[[Category: calcium binding protein]]
[[Category: penta-ef-hand protein]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 16:45:42 2007''

Latest revision as of 07:29, 7 February 2024

STRUCTURE OF APOPTOSIS-LINKED PROTEIN ALG-2

1hqv, resolution 2.30Å

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