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| | ==NMR Structure of the Cytoplasmic Tail of the Membrane Form of Heparin-binding EGF-like Growth Factor (proHB-EGF-CT) Complexed with the Ubiquitin Homology Domain of Bcl-2-associated Athanogene 1 from Mus musculus (mBAG-1-UBH)== | | ==NMR Structure of the Cytoplasmic Tail of the Membrane Form of Heparin-binding EGF-like Growth Factor (proHB-EGF-CT) Complexed with the Ubiquitin Homology Domain of Bcl-2-associated Athanogene 1 from Mus musculus (mBAG-1-UBH)== |
| - | <StructureSection load='2m8s' size='340' side='right' caption='[[2m8s]], [[NMR_Ensembles_of_Models | 18 NMR models]]' scene=''> | + | <StructureSection load='2m8s' size='340' side='right'caption='[[2m8s]], [[NMR_Ensembles_of_Models | 18 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2m8s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M8S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2M8S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2m8s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2M8S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2M8S FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bag1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), HBEGF, DTR, DTS, HEGFL ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Bag1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), HBEGF, DTR, DTS, HEGFL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2m8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8s OCA], [http://pdbe.org/2m8s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2m8s RCSB], [http://www.ebi.ac.uk/pdbsum/2m8s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8s 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=2m8s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2m8s OCA], [https://pdbe.org/2m8s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2m8s RCSB], [https://www.ebi.ac.uk/pdbsum/2m8s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2m8s ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/BAG1_MOUSE BAG1_MOUSE]] Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli.<ref>PMID:9873016</ref> [[http://www.uniprot.org/uniprot/HBEGF_HUMAN HBEGF_HUMAN]] Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor. | + | [[https://www.uniprot.org/uniprot/BAG1_MOUSE BAG1_MOUSE]] Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli.<ref>PMID:9873016</ref> [[https://www.uniprot.org/uniprot/HBEGF_HUMAN HBEGF_HUMAN]] Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2m8s" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2m8s" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[BAG family proteins 3D structures|BAG family proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Lk3 transgenic mice]] | | [[Category: Lk3 transgenic mice]] |
| | [[Category: Huang, H W]] | | [[Category: Huang, H W]] |
| Structural highlights
Function
[BAG1_MOUSE] Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli.[1] [HBEGF_HUMAN] Growth factor that mediates its effects via EGFR, ERBB2 and ERBB4. Required for normal cardiac valve formation and normal heart function. Promotes smooth muscle cell proliferation. May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts, but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF. Also acts as a diphtheria toxin receptor.
Publication Abstract from PubMed
The membrane form of heparin binding EGF-like growth factor (proHB-EGF) yields secreted HB-EGF and a membrane-anchored cytoplasmic tail (proHB-EGF-CT), which may be targeted to the nuclear membrane after a shedding stimulus. Bcl-2-associated athanogene 1 (BAG-1) accumulates in the nuclei and inhibits apoptosis in adenoma-derived cell lines. The maintenance of high levels of nuclear BAG-1 enhances cell survival. However, the ubiquitin homology domain of BAG-1 from Mus musculus (mBAG-1-UBH) is proposed to interact with proHB-EGF-CT, and this interaction may enhance the cytoprotection against the apoptosis inducer. The mechanism of the synergistic anti-apoptosis function of proHB-EGF-CT and mBAG-1-UBH is still unknown. We offer a hypothesis that proHB-EGF-CT can maintain high levels of nuclear BAG-1. In this study, we first report the three-dimensional nuclear magnetic resonance structure of proHB-EGF-CT complexed with mBAG-1-UBH. In the structure of the complex, the residues in the C-terminus and one turn between beta-strands beta1 and beta2 of mBAG-1-UBH bind to two terminals of proHB-EGF-CT, which folds into a loop with end-to-end contact. This end-to-end folding of proHB-EGF-CT causes the basic amino acids to colocalize and form a positively charged groove. The dominant forces in the binding interface between proHB-EGF-CT and mBAG-1-UBH are charge-charge interactions. On the basis of our mutagenesis results, the basic amino acid cluster in the N-terminus of proHB-EGF-CT is the crucial binding site for mBAG-1-UBH, whereas another basic amino acid in the C-terminus facilitates this interaction. Interestingly, the mBAG-1-UBH binding region on the proHB-EGF-CT peptide is also involved in the region found to be important for nuclear envelope targeting, supporting the hypothesis that proHB-EGF-CT is most likely able to trigger the nuclear translocation of BAG-1 in keeping its level high.
Nuclear Magnetic Resonance Structure of the Cytoplasmic Tail of Heparin Binding EGF-like Growth Factor (proHB-EGF-CT) Complexed with the Ubiquitin Homology Domain of Bcl-2-Associated Athanogene 1 from Mus musculus (mBAG-1-UBH).,Hung KW, Huang HW, Cho CC, Chang SC, Yu C Biochemistry. 2014 Apr 1;53(12):1935-46. doi: 10.1021/bi5003019. Epub 2014 Mar, 24. PMID:24628338[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Takayama S, Xie Z, Reed JC. An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators. J Biol Chem. 1999 Jan 8;274(2):781-6. PMID:9873016
- ↑ Hung KW, Huang HW, Cho CC, Chang SC, Yu C. Nuclear Magnetic Resonance Structure of the Cytoplasmic Tail of Heparin Binding EGF-like Growth Factor (proHB-EGF-CT) Complexed with the Ubiquitin Homology Domain of Bcl-2-Associated Athanogene 1 from Mus musculus (mBAG-1-UBH). Biochemistry. 2014 Apr 1;53(12):1935-46. doi: 10.1021/bi5003019. Epub 2014 Mar, 24. PMID:24628338 doi:http://dx.doi.org/10.1021/bi5003019
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