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5f74

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Revision as of 08:02, 29 April 2020

Crystal structure of ChREBP:14-3-3 complex bound with AMP

Structural highlights

5f74 is a 2 chain structure with sequence from Buffalo rat and Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	Ywhab (LK3 transgenic mice), Mlxipl, Wbscr14 (Buffalo rat)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[1433B_MOUSE] Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2 (By similarity). [MLXPL_RAT] Transcriptional repressor. Binds to the canonical and non-canonical E box sequences 5'-CACGTG-3' (By similarity).

Publication Abstract from PubMed

The carbohydrate responsive element-binding protein (ChREBP) is a glucose-responsive transcription factor that plays the essential role in converting excess carbohydrate to fat storage in the liver. In response to glucose level, ChREBP is regulated by nuclear/cytosol trafficking via interaction with either 14-3-3 proteins, CRM-1 (Exportin-1 or XPO-1), or importins. Nuclear localization of ChREBP was rapidly inhibited when incubated in branched-chain alpha-ketoacids, saturated and unsaturated fatty acids or AICAR. Here, we discovered that protein-free extracts of high fat-fed livers contained, in addition to ketone bodies, a new metabolite, identified as AMP, which specifically activates the interaction between ChREBP and 14-3-3. The crystal structure showed that AMP binds directly to the N-terminus of ChREBP-alpha2 helix. Our results suggest that AMP inhibits the nuclear localization of ChREBP through an allosteric activation of ChREBP/14-3-3 interactions, and not by activation of AMPK. AMP and ketone bodies together can therefore inhibit lipogenesis by restricting localization of ChREBP to the cytoplasm during periods of ketosis.

Metabolite Regulation of Nuclear Localization of Carbohydrate Response Element-binding Protein (ChREBP). Role of AMP as an Allosteric Inhibitor.,Sato S, Jung H, Nakagawa T, Pawlosky R, Takeshima T, Lee WR, Sakiyama H, Laxman S, Wynn RM, Tu B, MacMillan JB, De Brabander JK, Veech RL, Uyeda K J Biol Chem. 2016 Mar 16. pii: jbc.M115.708982. PMID:26984404^[1]

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

References

↑ Sato S, Jung H, Nakagawa T, Pawlosky R, Takeshima T, Lee WR, Sakiyama H, Laxman S, Wynn RM, Tu B, MacMillan JB, De Brabander JK, Veech RL, Uyeda K. Metabolite Regulation of Nuclear Localization of Carbohydrate Response Element-binding Protein (ChREBP). Role of AMP as an Allosteric Inhibitor. J Biol Chem. 2016 Mar 16. pii: jbc.M115.708982. PMID:26984404 doi:http://dx.doi.org/10.1074/jbc.M115.708982

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5f74"

@@ Line 1: / Line 1: @@
 ==Crystal structure of ChREBP:14-3-3 complex bound with AMP==
-<StructureSection load='5f74' size='340' side='right' caption='[[5f74]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
+<StructureSection load='5f74' size='340' side='right'caption='[[5f74]], [[Resolution|resolution]] 2.35&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5f74]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F74 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5F74 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5f74]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5F74 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5F74 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AMP:ADENOSINE+MONOPHOSPHATE'>AMP</scene></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=5f74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f74 OCA], [http://pdbe.org/5f74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f74 RCSB], [http://www.ebi.ac.uk/pdbsum/5f74 PDBsum]</span></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ywhab ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Mlxipl, Wbscr14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=5f74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5f74 OCA], [http://pdbe.org/5f74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5f74 RCSB], [http://www.ebi.ac.uk/pdbsum/5f74 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5f74 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 5f74" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Buffalo rat]]
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Jung, H]]
 [[Category: Uyeda, K]]

5f74

From Proteopedia

Revision as of 08:02, 29 April 2020

Crystal structure of ChREBP:14-3-3 complex bound with AMP

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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