2xa7: Difference between revisions

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[[Image:2xa7.png|left|200px]]


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==AP2 clathrin adaptor core in active complex with cargo peptides==
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<StructureSection load='2xa7' size='340' side='right'caption='[[2xa7]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2xa7]] is a 5 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=2XA7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XA7 FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
{{STRUCTURE_2xa7|  PDB=2xa7  |  SCENE= }}
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2xa7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xa7 OCA], [https://pdbe.org/2xa7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xa7 RCSB], [https://www.ebi.ac.uk/pdbsum/2xa7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xa7 ProSAT]</span></td></tr>
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== Function ==
[https://www.uniprot.org/uniprot/AP2S1_MOUSE AP2S1_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 and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).<ref>PMID:14745134</ref> <ref>PMID:15473838</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
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    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/xa/2xa7_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=2xa7 ConSurf].
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== Publication Abstract from PubMed ==
The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Using protein crystallography, we show that AP2 undergoes a large conformational change in which C-mu2 relocates to an orthogonal face of the complex, simultaneously unblocking both cargo-binding sites; the previously unstructured mu2 linker becomes helical and binds back onto the complex. This structural rearrangement results in AP2's four PtdIns4,5P(2)- and two endocytic motif-binding sites becoming coplanar, facilitating their simultaneous interaction with PtdIns4,5P(2)/cargo-containing membranes. Using a range of biophysical techniques, we show that the endocytic cargo binding of AP2 is driven by its interaction with PtdIns4,5P(2)-containing membranes.


===AP2 CLATHRIN ADAPTOR CORE IN ACTIVE COMPLEX WITH CARGO PEPTIDES===
A large-scale conformational change couples membrane recruitment to cargo binding in the AP2 clathrin adaptor complex.,Jackson LP, Kelly BT, McCoy AJ, Gaffry T, James LC, Collins BM, Honing S, Evans PR, Owen DJ Cell. 2010 Jun 25;141(7):1220-9. PMID:20603002<ref>PMID:20603002</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
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*[[Adaptin 3D structures|Adaptin 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 20603002 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_20603002}}
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</StructureSection>
==About this Structure==
2XA7 is a 5 chains structure with sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XA7 OCA].
 
==Reference==
<ref group="xtra">PMID:20603002</ref><references group="xtra"/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Rattus norvegicus]]
[[Category: Rattus norvegicus]]
[[Category: Evans, P R.]]
[[Category: Evans PR]]
[[Category: Jackson, L P.]]
[[Category: Jackson LP]]
[[Category: Kelly, B T.]]
[[Category: Kelly BT]]
[[Category: Mccoy, A J.]]
[[Category: McCoy AJ]]
[[Category: Owen, D J.]]
[[Category: Owen DJ]]
[[Category: Cell membrane]]
[[Category: Endocytosis]]
[[Category: Lipid-binding]]
[[Category: Phosphoprotein]]
[[Category: Protein transport]]
 
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