View source for 2jkr


==AP2 CLATHRIN ADAPTOR CORE with Dileucine peptide RM(phosphoS)QIKRLLSE==
<StructureSection load='2jkr' size='340' side='right'caption='[[2jkr]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2jkr]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2JKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2JKR 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]] 2.98&#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=SO4:SULFATE+ION'>SO4</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=2jkr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2jkr OCA], [https://pdbe.org/2jkr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2jkr RCSB], [https://www.ebi.ac.uk/pdbsum/2jkr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2jkr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AP2A2_MOUSE AP2A2_MOUSE] Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif.<ref>PMID:10459011</ref> <ref>PMID:14745134</ref> <ref>PMID:15473838</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/jk/2jkr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2jkr ConSurf].
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== Publication Abstract from PubMed ==
Most transmembrane proteins are selected as transport vesicle cargo through the recognition of short, linear amino acid motifs in their cytoplasmic portions by vesicle coat proteins. In the case of clathrin-coated vesicles (CCVs) the motifs are recognised by clathrin adaptors. The AP2 adaptor complex (subunits alpha,beta2,mu2,sigma2) recognises both major endocytic motifs: YxxPhi motifs and [DE]xxxL[LI] acidic dileucine motifs. Here we describe the binding of AP2 to the endocytic dileucine motif from CD4 . The major recognition events are the two leucine residues binding in hydrophobic pockets on sigma2. The hydrophilic residue four residues upstream from the first leucine sits on a positively charged patch made from residues on sigma2 and alpha subunits. Mutations in key residues inhibit the binding of AP2 to 'acidic dileucine' motifs displayed in liposomes containing PtdIns4,5P(2), but do not affect binding to YxxPhi motifs via mu2. In the 'inactive' AP2 core structure , both motif binding sites are blocked by different parts of the beta2 subunit. To allow a dileucine motif to bind, the beta2 N-terminus is displaced and becomes disordered; however, in this structure the YxxPhi binding site on mu2 remains blocked.

A structural explanation for the binding of endocytic dileucine motifs by the AP2 complex.,Kelly BT, McCoy AJ, Spate K, Miller SE, Evans PR, Honing S, Owen DJ Nature. 2008 Dec 18;456(7224):976-979. doi: 10.1038/nature07422. PMID:19140243<ref>PMID:19140243</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 2jkr" style="background-color:#fffaf0;"></div>

==See Also==
*[[Adaptin 3D structures|Adaptin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Evans PR]]
[[Category: Kelly BT]]
[[Category: McCoy AJ]]
[[Category: Owen DJ]]