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| | <StructureSection load='6fbx' size='340' side='right'caption='[[6fbx]], [[Resolution|resolution]] 1.64Å' scene=''> | | <StructureSection load='6fbx' size='340' side='right'caption='[[6fbx]], [[Resolution|resolution]] 1.64Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6fbx]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FBX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FBX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fbx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FBX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6FBX FirstGlance]. <br> |
| - | </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=6fbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fbx OCA], [http://pdbe.org/6fbx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fbx RCSB], [http://www.ebi.ac.uk/pdbsum/6fbx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fbx 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]] 1.639Å</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=6fbx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fbx OCA], [https://pdbe.org/6fbx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6fbx RCSB], [https://www.ebi.ac.uk/pdbsum/6fbx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6fbx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6fbx" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6fbx" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[B-cell lymphoma proteins 3D structures|B-cell lymphoma proteins 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Danio rerio]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hinds, M G]] | + | [[Category: Hinds MG]] |
| - | [[Category: Kvansakul, M]] | + | [[Category: Kvansakul M]] |
| - | [[Category: Suraweera, C D]] | + | [[Category: Suraweera CD]] |
| - | [[Category: Apoptosis]]
| + | |
| - | [[Category: Bcl-2 family]]
| + | |
| - | [[Category: Pro-survival protein]]
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| Structural highlights
Publication Abstract from PubMed
Bcl-2 family proteins play a crucial role in regulating apoptosis, a process critical for development, eliminating damaged or infected cells, host-pathogen interactions and in disease. Dysregulation of Bcl-2 proteins elicits an expansive cell survival mechanism promoting cell migration, invasion and metastasis. Through a network of intra-family protein-protein interactions Bcl-2 family members regulate the release of cell death factors from mitochondria. NRZ is a novel zebrafish pro-survival Bcl-2 orthologue resident on mitochondria and the endoplasmic reticulum (ER). However, the mechanism of NRZ apoptosis inhibition has not yet been clarified. Here we examined the interactions of NRZ with pro-apoptotic members of the Bcl-2 family using a combination of isothermal calorimetry and mutational analysis of NRZ. We show that NRZ binds almost all zebrafish pro-apoptotic proteins and displays a broad range of affinities. Furthermore, we define the structural basis for apoptosis inhibition of NRZ by solving the crystal structure of both apo-NRZ and a holo form bound to a peptide spanning the binding motif of the pro-apoptotic zBad, a BH3-only protein orthologous to mammalian Bad. The crystal structure of NRZ revealed that it adopts the conserved Bcl-2 like fold observed for other cellular pro-survival Bcl-2 proteins and employs the canonical ligand binding groove to bind Bad BH3 peptide. NRZ engagement of Bad BH3 involves the canonical ionic interaction between NRZ R86 and Bad D104 and an additional ionic interaction between NRZ D79 and Bad R100, and substitution of either NRZ R86 or D79 to Ala reduces the binding to Bad BH3 tenfold or more. Our findings provide a detailed mechanistic understanding for NRZ mediated anti-apoptotic activity in zebrafish by revealing binding to both Bad and Noxa, suggesting that NRZ is likely to occupy a unique mechanistic role in zebrafish apoptosis regulation by acting as a highly promiscuous pro-apoptotic Bcl-2 binder.
A structural investigation of NRZ mediated apoptosis regulation in zebrafish.,Suraweera CD, Caria S, Jarva M, Hinds MG, Kvansakul M Cell Death Dis. 2018 Sep 20;9(10):967. doi: 10.1038/s41419-018-0992-0. PMID:30237469[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Suraweera CD, Caria S, Jarva M, Hinds MG, Kvansakul M. A structural investigation of NRZ mediated apoptosis regulation in zebrafish. Cell Death Dis. 2018 Sep 20;9(10):967. doi: 10.1038/s41419-018-0992-0. PMID:30237469 doi:http://dx.doi.org/10.1038/s41419-018-0992-0
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