2g30

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{{STRUCTURE_2g30| PDB=2g30 | SCENE= }}
 
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===beta appendage of AP2 complexed with ARH peptide===
 
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{{ABSTRACT_PUBMED_16516836}}
 
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==Disease==
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==beta appendage of AP2 complexed with ARH peptide==
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[[http://www.uniprot.org/uniprot/ARH_HUMAN ARH_HUMAN]] Defects in LDLRAP1 are the cause of autosomal recessive hypercholesterolemia (ARH) [MIM:[http://omim.org/entry/603813 603813]]. ARH is a disorder caused by defective internalization of LDL receptors (LDLR) in the liver. ARH has the clinical features of familial hypercholesterolemia (FH) [MIM:[http://omim.org/entry/143890 143890]] homozygotes, including severely elevated plasma LDL cholesterol, tuberous and tendon xanthomata, and premature atherosclerosis. LDL receptor (LDLR) activity measured in skin fibroblasts is normal, as the LDL binding ability.<ref>PMID:11326085</ref>
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<StructureSection load='2g30' size='340' side='right'caption='[[2g30]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2g30]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2007 RCSB PDB [https://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Clathrin'' by Graham T. Johnson and David S. Goodsell is [https://dx.doi.org/10.2210/rcsb_pdb/mom_2007_4 10.2210/rcsb_pdb/mom_2007_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G30 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2G30 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]] 1.6&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2g30 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g30 OCA], [https://pdbe.org/2g30 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2g30 RCSB], [https://www.ebi.ac.uk/pdbsum/2g30 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2g30 ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/AP2B1_HUMAN AP2B1_HUMAN] 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 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly.<ref>PMID:14745134</ref> <ref>PMID:15473838</ref> <ref>PMID:14985334</ref> <ref>PMID:19033387</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/g3/2g30_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=2g30 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Clathrin-associated sorting proteins (CLASPs) expand the repertoire of endocytic cargo sorted into clathrin-coated vesicles beyond the transmembrane proteins that bind physically to the AP-2 adaptor. LDL and GPCRs are internalized by ARH and beta-arrestin, respectively. We show that these two CLASPs bind selectively to the AP-2 beta2 appendage platform via an alpha-helical [DE](n)X(1-2)FXX[FL]XXXR motif, and that this motif also occurs and is functional in the epsins. In beta-arrestin, this motif maintains the endocytosis-incompetent state by binding back on the folded core of the protein in a beta strand conformation. Triggered via a beta-arrestin/GPCR interaction, the motif must be displaced and must undergo a strand to helix transition to enable the beta2 appendage binding that drives GPCR-beta-arrestin complexes into clathrin coats. Another interaction surface on the beta2 appendage sandwich is identified for proteins such as eps15 and clathrin, suggesting a mechanism by which clathrin displaces eps15 to lattice edges during assembly.
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==Function==
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Molecular switches involving the AP-2 beta2 appendage regulate endocytic cargo selection and clathrin coat assembly.,Edeling MA, Mishra SK, Keyel PA, Steinhauser AL, Collins BM, Roth R, Heuser JE, Owen DJ, Traub LM Dev Cell. 2006 Mar;10(3):329-42. PMID:16516836<ref>PMID:16516836</ref>
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[[http://www.uniprot.org/uniprot/AP2B1_HUMAN AP2B1_HUMAN]] 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 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly.<ref>PMID:14745134</ref><ref>PMID:15473838</ref><ref>PMID:14985334</ref><ref>PMID:19033387</ref> [[http://www.uniprot.org/uniprot/ARH_HUMAN ARH_HUMAN]] Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts). May be required for LDL binding and internalization but not for receptor clustering in coated pits. May facilitate the endocytocis of LDLR and LDLR-LDL complexes from coated pits by stabilizing the interaction between the receptor and the structural components of the pits. May also be involved in the internalization of other LDLR family members. Binds to phosphoinositides, which regulate clathrin bud assembly at the cell surface.<ref>PMID:15728179</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[2g30]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. The April 2007 RCSB PDB [http://pdb.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/index.html Molecule of the Month] feature on ''Clathrin'' by Graham T. Johnson and David S. Goodsell is [http://dx.doi.org/10.2210/rcsb_pdb/mom_2007_4 10.2210/rcsb_pdb/mom_2007_4]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G30 OCA].
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</div>
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<div class="pdbe-citations 2g30" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:016516836</ref><ref group="xtra">PMID:016697009</ref><ref group="xtra">PMID:019696796</ref><references group="xtra"/><references/>
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*[[Adaptin 3D structures|Adaptin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Clathrin]]
[[Category: Clathrin]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Large Structures]]
[[Category: RCSB PDB Molecule of the Month]]
[[Category: RCSB PDB Molecule of the Month]]
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[[Category: Collins, B M.]]
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[[Category: Collins BM]]
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[[Category: Edeling, M A.]]
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[[Category: Edeling MA]]
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[[Category: Owen, D J.]]
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[[Category: Owen DJ]]
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[[Category: Traub, L M.]]
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[[Category: Traub LM]]
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[[Category: Adaptor]]
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[[Category: Alpha-helical arh peptide]]
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[[Category: Endocytosis]]
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[[Category: Endocytosis-exocytosis complex]]
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[[Category: Platform domain]]
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[[Category: Sandwich domain]]
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Current revision

beta appendage of AP2 complexed with ARH peptide

PDB ID 2g30

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