5fcg

From Proteopedia

(Difference between revisions)

Current revision

Crystal structure of Bcl-2 in complex with HBx-BH3 motif

Structural highlights

5fcg is a 2 chain structure with sequence from Hepatitis B virus and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

BCL2_HUMAN Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.

Function

BCL2_HUMAN Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).^[1]

Publication Abstract from PubMed

HBx is a hepatitis B virus protein that is required for viral infectivity and replication. Anti-apoptotic Bcl-2 family members are thought to be among the important host targets of HBx. However, the structure and function of HBx are poorly understood and the molecular mechanism of HBx-induced carcinogenesis remains unknown. In this study, we report biochemical and structural characterization of HBx. The recombinant HBx protein contains metal ions, in particular iron and zinc. A BH3-like motif in HBx (residues 110-135) binds Bcl-2 with a dissociation constant of approximately 193 muM, which is drastically lower than that for a canonical BH3 motif from Bim or Bad. Structural analysis reveals that, similar to other BH3 motifs, the BH3-like motif of HBx adopts an amphipathic alpha-helix and binds the conserved BH3-binding groove on Bcl-2. Unlike the helical Bim or Bad BH3 motif, the C-terminal portion of the bound HBx BH3-like motif has an extended conformation and makes considerably fewer interactions with Bcl-2. These observations suggest that HBx may modulate Bcl-2 function in a way that is different from that of the classical BH3-only proteins.

Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx.,Jiang T, Liu M, Wu J, Shi Y Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2074-9. doi:, 10.1073/pnas.1525616113. Epub 2016 Feb 8. PMID:26858413^[2]

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

References

↑ Wei Y, Pattingre S, Sinha S, Bassik M, Levine B. JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell. 2008 Jun 20;30(6):678-88. doi: 10.1016/j.molcel.2008.06.001. PMID:18570871 doi:10.1016/j.molcel.2008.06.001
↑ Jiang T, Liu M, Wu J, Shi Y. Structural and biochemical analysis of Bcl-2 interaction with the hepatitis B virus protein HBx. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2074-9. doi:, 10.1073/pnas.1525616113. Epub 2016 Feb 8. PMID:26858413 doi:http://dx.doi.org/10.1073/pnas.1525616113

1 Structural highlights
2 Disease
3 Function
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/5fcg"

@@ Line 3: / Line 3: @@
 <StructureSection load='5fcg' size='340' side='right'caption='[[5fcg]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5fcg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FCG OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5FCG FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5fcg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepatitis_B_virus Hepatitis B virus] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5FCG FirstGlance]. <br>
-</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5fcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fcg OCA], [http://pdbe.org/5fcg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fcg RCSB], [http://www.ebi.ac.uk/pdbsum/5fcg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5fcg ProSAT]</span></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]] 2.1&#8491;</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=5fcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fcg OCA], [https://pdbe.org/5fcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5fcg RCSB], [https://www.ebi.ac.uk/pdbsum/5fcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5fcg ProSAT]</span></td></tr>
 </table>
+== Disease ==
+[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Note=A chromosomal aberration involving BCL2 has been found in chronic lymphatic leukemia. Translocation t(14;18)(q32;q21) with immunoglobulin gene regions. BCL2 mutations found in non-Hodgkin lymphomas carrying the chromosomal translocation could be attributed to the Ig somatic hypermutation mechanism resulting in nucleotide transitions.
 == Function ==
-[[http://www.uniprot.org/uniprot/E9L5H4_HBV E9L5H4_HBV]] Multifunctional protein that may modulate protein degradation pathways, apoptosis, transcription, signal transduction, cell cycle progress, and genetic stability by directly or indirectly interacting with host factors.[RuleBase:RU361181]
+[https://www.uniprot.org/uniprot/BCL2_HUMAN BCL2_HUMAN] Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).<ref>PMID:18570871</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Hepatitis B virus]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Jiang, T Y]]
+[[Category: Jiang TY]]
-[[Category: Liu, M H]]
+[[Category: Liu MH]]
-[[Category: Shi, Y G]]
+[[Category: Shi YG]]
-[[Category: Wu, J P]]
+[[Category: Wu JP]]
-[[Category: Apoptosis]]
-[[Category: Complex]]

5fcg

From Proteopedia

Current revision

Crystal structure of Bcl-2 in complex with HBx-BH3 motif

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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