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| | ==Solution structure of the transmembrane domain of Bcl-2 member Harakiri in micelles== | | ==Solution structure of the transmembrane domain of Bcl-2 member Harakiri in micelles== |
| - | <StructureSection load='2l5b' size='340' side='right'caption='[[2l5b]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l5b' size='340' side='right'caption='[[2l5b]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l5b]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l5b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L5B FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=2l5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5b OCA], [https://pdbe.org/2l5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5b RCSB], [https://www.ebi.ac.uk/pdbsum/2l5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5b 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=2l5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5b OCA], [https://pdbe.org/2l5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l5b RCSB], [https://www.ebi.ac.uk/pdbsum/2l5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l5b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/HRK_HUMAN HRK_HUMAN]] Promotes apoptosis.<ref>PMID:15031724</ref> <ref>PMID:9130713</ref>
| + | [https://www.uniprot.org/uniprot/HRK_HUMAN HRK_HUMAN] Promotes apoptosis.<ref>PMID:15031724</ref> <ref>PMID:9130713</ref> |
| | <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: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Alba, E de]]
| + | [[Category: Barrera-Vilarmau S]] |
| - | [[Category: Barrera-Vilarmau, S]] | + | [[Category: Obregon P]] |
| - | [[Category: Obregon, P]] | + | [[Category: De Alba E]] |
| - | [[Category: Apoptosis]] | + | |
| - | [[Category: Bcl-2]]
| + | |
| - | [[Category: Bh3-only]]
| + | |
| - | [[Category: Harakiri]]
| + | |
| - | [[Category: Transmembrane domain]]
| + | |
| Structural highlights
Function
HRK_HUMAN Promotes apoptosis.[1] [2]
Publication Abstract from PubMed
Harakiri is a BH3-only member of the Bcl-2 family that localizes in membranes and induces cell death by binding to prosurvival Bcl-x(L) and Bcl-2. The cytosolic domain of Harakiri is largely disorder with residual alpha-helical conformation according to previous structural studies. As these helical structures could play an important role in Harakiri's function, we have used NMR and circular dichroism to fully characterize them at the residue-atomic level. In addition, we report structural studies on a peptide fragment spanning Harakiri's C-terminal hydrophobic sequence, which potentially operates as a transmembrane domain. We initially checked by enzyme immunoassays and NMR that peptides encompassing different lengths of the cytosolic domain are functional as they bind Bcl-x(L) and Bcl-2. The structural data in water indicate that the alpha-helical conformation is restricted to a 25-residue segment comprising the BH3 domain. However, structure calculation was precluded because of insufficient NMR restraints. To bypass this problem we used alcohol-water mixture to increase structure population and confirmed by NMR that the conformation in both milieus is equivalent. The resulting three-dimensional structure closely resembles that of peptides encompassing the BH3 domain of BH3-only members in complex with their prosurvival partners, suggesting that preformed structural elements in the disordered protein are central to binding. In contrast, the transmembrane domain forms in micelles a monomeric alpha-helix with a population close to 100%. Its three-dimensional structure here reported reveals features that explain its function as membrane anchor. Altogether these results are used to propose a tentative structural model of how Harakiri works.
Intrinsic order and disorder in the bcl-2 member harakiri: insights into its proapoptotic activity.,Barrera-Vilarmau S, Obregon P, de Alba E PLoS One. 2011;6(6):e21413. Epub 2011 Jun 23. PMID:21731739[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sunayama J, Ando Y, Itoh N, Tomiyama A, Sakurada K, Sugiyama A, Kang D, Tashiro F, Gotoh Y, Kuchino Y, Kitanaka C. Physical and functional interaction between BH3-only protein Hrk and mitochondrial pore-forming protein p32. Cell Death Differ. 2004 Jul;11(7):771-81. PMID:15031724 doi:http://dx.doi.org/10.1038/sj.cdd.4401418
- ↑ Inohara N, Ding L, Chen S, Nunez G. harakiri, a novel regulator of cell death, encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L). EMBO J. 1997 Apr 1;16(7):1686-94. PMID:9130713 doi:http://dx.doi.org/10.1093/emboj/16.7.1686
- ↑ Barrera-Vilarmau S, Obregon P, de Alba E. Intrinsic order and disorder in the bcl-2 member harakiri: insights into its proapoptotic activity. PLoS One. 2011;6(6):e21413. Epub 2011 Jun 23. PMID:21731739 doi:10.1371/journal.pone.0021413
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