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3cva

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Revision as of 22:00, 25 December 2014

Human Bcl-xL containing a Trp to Ala mutation at position 137

Structural highlights

3cva is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	bcl-xl (Homo sapiens)
Resources:	FirstGlance, OCA, RCSB, PDBsum

Function

[BCLX_HUMAN] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.^[1] ^[2] Isoform Bcl-X(S) promotes apoptosis.^[3] ^[4]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Bcl-2 family proteins regulate apoptosis through their homo- and heterodimerization. By protein sequence analysis and structural comparison, we have identified a conserved hydrophobic core at the BH1 and BH2 domains of Bcl-2 family proteins. The hydrophobic core is stabilized by hydrophobic interactions among the residues of Trp137, Ile140, Trp181, Ile182, Trp188 and Phe191 in Bcl-x(L). Destabilization of the hydrophobic core can promote the protein unfolding and pore formation in synthetic lipid vesicles. Interestingly, though the hydrophobic core does not participate in binding with BH3 domain of pro-apoptotic proteins, disruption of the hydrophobic core can reduce the affinity of Bcl-x(L) with BH3-domain peptide by changing the conformation of Bcl-x(L) C-terminal residues that are involved in the peptide interaction. The BH3-domain peptide binding affinity and pore forming propensity of Bcl-x(L) were correlated to its death-repressor activity, which provides new information to help study the regulatory mechanism of anti-apoptotic proteins. Meanwhile, as the tryptophans are conserved in the hydrophobic core, in vitro binding assay based on FRET of "Trp-->AEDANS" can be devised to screen for new modulators targeting anti-apoptotic proteins as well as "multi-BH domains" pro-apoptotic proteins.

A conserved hydrophobic core at Bcl-xL mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein.,Feng Y, Zhang L, Hu T, Shen X, Ding J, Chen K, Jiang H, Liu D Arch Biochem Biophys. 2009 Apr 1;484(1):46-54. Epub 2009 Jan 10. PMID:19161970^[5]

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

References

↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Terrano DT, Upreti M, Chambers TC. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Mol Cell Biol. 2010 Feb;30(3):640-56. doi: 10.1128/MCB.00882-09. Epub 2009 Nov, 16. PMID:19917720 doi:10.1128/MCB.00882-09
↑ Wang J, Beauchemin M, Bertrand R. Bcl-xL phosphorylation at Ser49 by polo kinase 3 during cell cycle progression and checkpoints. Cell Signal. 2011 Dec;23(12):2030-8. doi: 10.1016/j.cellsig.2011.07.017. Epub, 2011 Aug 5. PMID:21840391 doi:10.1016/j.cellsig.2011.07.017
↑ Feng Y, Zhang L, Hu T, Shen X, Ding J, Chen K, Jiang H, Liu D. A conserved hydrophobic core at Bcl-xL mediates its structural stability and binding affinity with BH3-domain peptide of pro-apoptotic protein. Arch Biochem Biophys. 2009 Apr 1;484(1):46-54. Epub 2009 Jan 10. PMID:19161970 doi:10.1016/j.abb.2009.01.003

1 Structural highlights
2 Function
3 Evolutionary Conservation
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/3cva"

@@ Line 6: / Line 6: @@
 <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=3cva FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cva OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3cva RCSB], [http://www.ebi.ac.uk/pdbsum/3cva PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/BCLX_HUMAN BCLX_HUMAN]] Potent inhibitor of cell death. Inhibits activation of caspases (By similarity). Appears to regulate cell death by blocking the voltage-dependent anion channel (VDAC) by binding to it and preventing the release of the caspase activator, CYC1, from the mitochondrial membrane. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>   Isoform Bcl-X(S) promotes apoptosis.<ref>PMID:19917720</ref> <ref>PMID:21840391</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 32: / Line 34: @@
 </StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Chen, K.]]
+[[Category: Chen, K]]
-[[Category: Feng, Y.]]
+[[Category: Feng, Y]]
-[[Category: Hu, T.]]
+[[Category: Hu, T]]
-[[Category: Jiang, H.]]
+[[Category: Jiang, H]]
-[[Category: Liu, D.]]
+[[Category: Liu, D]]
-[[Category: Shen, X.]]
+[[Category: Shen, X]]
-[[Category: Zhang, L.]]
+[[Category: Zhang, L]]
 [[Category: Apoptosis]]
 [[Category: Membrane]]

3cva

From Proteopedia

Revision as of 22:00, 25 December 2014

Human Bcl-xL containing a Trp to Ala mutation at position 137

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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