2m8s

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Revision as of 14:49, 10 September 2015

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)

Structural highlights

2m8s is a 2 chain structure with sequence from Human and Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	Bag1 (LK3 transgenic mice), HBEGF, DTR, DTS, HEGFL (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum

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.

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

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/2m8s"

@@ Line 4: / Line 4: @@
 <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>
 </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>
-<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://www.rcsb.org/pdb/explore.do?structureId=2m8s RCSB], [http://www.ebi.ac.uk/pdbsum/2m8s 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=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]</span></td></tr>
 </table>
 == Function ==
@@ Line 16: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 2m8s" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

2m8s

From Proteopedia

Revision as of 14:49, 10 September 2015

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)

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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