View source for 5yqg


==The structure of 14-3-3 and pNumb peptide==
<StructureSection load='5yqg' size='340' side='right'caption='[[5yqg]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5yqg]] is a 6 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=5YQG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YQG 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]] 2.1&#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></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=5yqg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5yqg OCA], [https://pdbe.org/5yqg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5yqg RCSB], [https://www.ebi.ac.uk/pdbsum/5yqg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5yqg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/1433F_MOUSE 1433F_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. Negatively regulates the kinase activity of PDPK1 (By similarity).
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== Publication Abstract from PubMed ==
Traffic of cargo across membranes helps establish, maintain, and reorganize distinct cellular compartments and is fundamental to many metabolic processes. The cargo-selective endocytic adaptor Numb participates in clathrin-dependent endocytosis by attaching cargoes to the clathrin adaptor alpha-adaptin. The phosphorylation of Numb at Ser(265) and Ser(284) recruits the regulatory protein 14-3-3, accompanied by the dissociation of Numb from alpha-adaptin and Numb's translocation from the cortical membrane to the cytosol. However, the molecular mechanisms underlying the Numb-alpha-adaptin interaction and its regulation by Numb phosphorylation and 14-3-3 recruitment remain poorly understood. Here, biochemical and structural analyses of the Numb.14-3-3 complex revealed that Numb phosphorylation at both Ser(265) and Ser(284) is required for Numb's efficient interaction with 14-3-3. We also discovered that an RQFRF motif surrounding Ser(265) in Numb functions together with the canonical C-terminal DPF motif, required for Numb's interaction with alpha-adaptin, to form a stable complex with alpha-adaptin. Of note, we provide evidence that the phosphorylation-induced binding of 14-3-3 to Numb directly competes with the binding of alpha-adaptin to Numb. Our findings suggest a potential mechanism governing the dynamic assembly of Numb with alpha-adaptin or 14-3-3. This dual-site recognition of Numb by alpha-adaptin may have implications for other alpha-adaptin targets. We propose that the newly identified alpha-adaptin-binding site surrounding Ser(265) in Numb functions as a triggering mechanism for the dynamic dissociation of the Numb.alpha-adaptin complex.

Structural determinants controlling 14-3-3 recruitment to the endocytic adaptor Numb and dissociation of the Numb.alpha-adaptin complex.,Chen X, Liu Z, Shan Z, Yao W, Gu A, Wen W J Biol Chem. 2018 Mar 16;293(11):4149-4158. doi: 10.1074/jbc.RA117.000897. Epub, 2018 Jan 30. PMID:29382713<ref>PMID:29382713</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5yqg" style="background-color:#fffaf0;"></div>

==See Also==
*[[14-3-3 protein 3D structures|14-3-3 protein 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Chen X]]
[[Category: Liu Z]]
[[Category: Wen W]]