|
|
| (4 intermediate revisions not shown.) |
| Line 1: |
Line 1: |
| | + | |
| | ==Crystal structure of cell death-inducing DFFA-like effector c== | | ==Crystal structure of cell death-inducing DFFA-like effector c== |
| - | <StructureSection load='4ikg' size='340' side='right' caption='[[4ikg]], [[Resolution|resolution]] 1.93Å' scene=''> | + | <StructureSection load='4ikg' size='340' side='right'caption='[[4ikg]], [[Resolution|resolution]] 1.93Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ikg]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IKG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IKG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ikg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IKG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IKG FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene><br> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9318Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ikg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ikg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ikg RCSB], [http://www.ebi.ac.uk/pdbsum/4ikg PDBsum]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> |
| - | <table> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ikg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ikg OCA], [https://pdbe.org/4ikg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ikg RCSB], [https://www.ebi.ac.uk/pdbsum/4ikg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ikg ProSAT]</span></td></tr> |
| - | <div style="background-color:#fffaf0;">
| + | </table> |
| - | == Publication Abstract from PubMed == | + | == Function == |
| - | Mature white adipocytes contain a characteristic unilocular lipid droplet. However, the molecular mechanisms underlying unilocular lipid droplet formation are poorly understood. We previously showed that Fsp27, an adipocyte-specific lipid droplet-associated protein, promotes lipid droplet growth by initiating lipid exchange and transfer. Here, we identify Perilipin1 (Plin1), another adipocyte-specific lipid droplet-associated protein, as an Fsp27 activator. Plin1 interacts with the CIDE-N domain of Fsp27 and markedly increases Fsp27-mediated lipid exchange, lipid transfer and lipid droplet growth. Functional cooperation between Plin1 and Fsp27 is required for efficient lipid droplet growth in adipocytes, as depletion of either protein impairs lipid droplet growth. The CIDE-N domain of Fsp27 forms homodimers and disruption of CIDE-N homodimerization abolishes Fsp27-mediated lipid exchange and transfer. Interestingly, Plin1 can restore the activity of CIDE-N homodimerization-defective mutants of Fsp27. We thus uncover a novel mechanism underlying lipid droplet growth and unilocular lipid droplet formation that involves the cooperative action of Fsp27 and Plin1 in adipocytes.
| + | [https://www.uniprot.org/uniprot/CIDEC_MOUSE CIDEC_MOUSE] Binds to lipid droplets and regulates their enlargement, thereby restricting lipolysis and favoring storage. At focal contact sites between lipid droplets, promotes directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair. Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1. May act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment. As mature adipocytes, that express high CIDEC levels, are quite resistant to apoptotic stimuli, the physiological significance of its role in apoptosis is unclear. May play a role in the modulation of the response to osmotic stress by preventing NFAT5 to translocate into the nucleus and activate its target genes expression.<ref>PMID:18334488</ref> <ref>PMID:22144693</ref> <ref>PMID:22245780</ref> <ref>PMID:23481402</ref> |
| - | | + | |
| - | Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes.,Sun Z, Gong J, Wu H, Xu W, Wu L, Xu D, Gao J, Wu JW, Yang H, Yang M, Li P Nat Commun. 2013;4:1594. doi: 10.1038/ncomms2581. PMID:23481402<ref>PMID:23481402</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Gao, J.]] | + | [[Category: Large Structures]] |
| - | [[Category: Yang, M.]] | + | [[Category: Mus musculus]] |
| - | [[Category: Apoptosis]] | + | [[Category: Gao J]] |
| - | [[Category: Cell death]] | + | [[Category: Yang M]] |
| - | [[Category: Fsp27]]
| + | |
| Structural highlights
Function
CIDEC_MOUSE Binds to lipid droplets and regulates their enlargement, thereby restricting lipolysis and favoring storage. At focal contact sites between lipid droplets, promotes directional net neutral lipid transfer from the smaller to larger lipid droplets. The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair. Its role in neutral lipid transfer and lipid droplet enlargement is activated by the interaction with PLIN1. May act as a CEBPB coactivator in the white adipose tissue to control the expression of a subset of CEBPB downstream target genes, including SOCS1, SOCS3, TGFB1, TGFBR1, ID2 and XDH. When overexpressed in preadipocytes, induces apoptosis or increases cell susceptibility to apoptosis induced by serum deprivation or TGFB treatment. As mature adipocytes, that express high CIDEC levels, are quite resistant to apoptotic stimuli, the physiological significance of its role in apoptosis is unclear. May play a role in the modulation of the response to osmotic stress by preventing NFAT5 to translocate into the nucleus and activate its target genes expression.[1] [2] [3] [4]
References
- ↑ Keller P, Petrie JT, De Rose P, Gerin I, Wright WS, Chiang SH, Nielsen AR, Fischer CP, Pedersen BK, MacDougald OA. Fat-specific protein 27 regulates storage of triacylglycerol. J Biol Chem. 2008 May 23;283(21):14355-65. doi: 10.1074/jbc.M708323200. Epub 2008, Mar 11. PMID:18334488 doi:http://dx.doi.org/10.1074/jbc.M708323200
- ↑ Gong J, Sun Z, Wu L, Xu W, Schieber N, Xu D, Shui G, Yang H, Parton RG, Li P. Fsp27 promotes lipid droplet growth by lipid exchange and transfer at lipid droplet contact sites. J Cell Biol. 2011 Dec 12;195(6):953-63. doi: 10.1083/jcb.201104142. Epub 2011 Dec, 5. PMID:22144693 doi:http://dx.doi.org/10.1083/jcb.201104142
- ↑ Wang W, Lv N, Zhang S, Shui G, Qian H, Zhang J, Chen Y, Ye J, Xie Y, Shen Y, Wenk MR, Li P. Cidea is an essential transcriptional coactivator regulating mammary gland secretion of milk lipids. Nat Med. 2012 Jan 15;18(2):235-43. doi: 10.1038/nm.2614. PMID:22245780 doi:http://dx.doi.org/10.1038/nm.2614
- ↑ Sun Z, Gong J, Wu H, Xu W, Wu L, Xu D, Gao J, Wu JW, Yang H, Yang M, Li P. Perilipin1 promotes unilocular lipid droplet formation through the activation of Fsp27 in adipocytes. Nat Commun. 2013;4:1594. doi: 10.1038/ncomms2581. PMID:23481402 doi:http://dx.doi.org/10.1038/ncomms2581
|
