View source for 29ii


==Structure of 14-3-3 epsilon in complex with a peptide derived from AMPK gamma 2==
<StructureSection load='29ii' size='340' side='right'caption='[[29ii]], [[Resolution|resolution]] 2.17&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[29ii]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=29II OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=29II FirstGlance]. <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]] 2.17&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></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=29ii FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=29ii OCA], [https://pdbe.org/29ii PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=29ii RCSB], [https://www.ebi.ac.uk/pdbsum/29ii PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=29ii ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/1433E_HUMAN 1433E_HUMAN] Distal 17p13.3 microdeletion syndrome;17p13.3 microduplication syndrome;Miller-Dieker syndrome. 
== Function ==
[https://www.uniprot.org/uniprot/1433E_HUMAN 1433E_HUMAN] 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.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
AMP-activated protein kinase (AMPK) plays an important role in maintaining energy homeostasis in mammals. AMPK is a heterotrimer of an alpha catalytic subunit and two regulatory subunits, beta and gamma. In mammals, each subunit has different isoforms (alpha1/alpha2, beta1/ beta2, and gamma1/gamma2/gamma3) encoded by separate genes, leading to the potential expression of 12 AMPK complexes. Here, we show that AMPK containing the long forms of gamma2 (gamma2a, encoding a protein of 569 amino acids, and gamma2c, 525 amino acids) binds to 14-3-3. In contrast to AMPK containing the short form of gamma2 (gamma2b, 328 amino acids), bacterial expression of AMPK containing the long forms of gamma2 requires co-expression with 14-3-3 and prior phosphorylation of Thr172 within the alpha subunit. AMPKgamma2-14-3-3 complexes have reduced activity compared with AMPKgamma1 or AMPKgamma2b but retain allosteric activation by AMP and the AMPK activator, 991. We found that two predicted 14-3-3 binding sites within gamma2a (T97 and S122) were phosphorylated in the bacterially expressed AMPK complex. Furthermore, we show that a peptide spanning these two phosphorylated sites binds to 14-3-3 in vitro and determined the crystal structure of this 14-3-3-peptide co-complex. These results indicate that 14-3-3 binds to the N-terminal region of gamma2a/c, reducing the activity of AMPK relative to AMPKgamma1 and AMPKgamma2b. Our findings reveal a new mode of regulation of AMPK containing the long forms of gamma2. While the biological significance of 14-3-3 binding to AMPKgamma2a/c complexes remains to be determined, our studies provide the starting point to begin to address this issue.

Binding of 14-3-3 stabilises recombinant AMPKgamma2-containing complexes.,Chen SY, Bennett J, Navaratnam N, Fiadeiro R, Woods A, Montoya A, Shliaha PV, Kunzelmann S, Howell SA, Mehmood S, Purkiss AG, Wilson JR, Gamblin SJ, Carling D Biochem J. 2026 May 6;483(5):621-637. doi: 10.1042/BCJ20250342. PMID:41873906<ref>PMID:41873906</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 29ii" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Carling D]]
[[Category: Chen S]]
[[Category: Gamblin SJ]]
[[Category: Purkiss A]]
[[Category: Wilson JR]]