This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2l5b

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 17:28, 10 September 2015

Solution structure of the transmembrane domain of Bcl-2 member Harakiri in micelles

Structural highlights

2l5b is a 1 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l5b"

@@ Line 4: / Line 4: @@
 <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 [http://oca.weizmann.ac.il/oca-docs/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>
-<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=2l5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5b OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2l5b RCSB], [http://www.ebi.ac.uk/pdbsum/2l5b 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=2l5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l5b OCA], [http://pdbe.org/2l5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l5b RCSB], [http://www.ebi.ac.uk/pdbsum/2l5b PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/HRK_HUMAN HRK_HUMAN]] Promotes apoptosis.<ref>PMID:15031724</ref> <ref>PMID:9130713</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2l5b" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2l5b

From Proteopedia

Revision as of 17:28, 10 September 2015

Solution structure of the transmembrane domain of Bcl-2 member Harakiri in micelles

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox