View source for 2pku


==Solution structure of PICK1 PDZ in complex with the carboxyl tail peptide of GluR2==
<StructureSection load='2pku' size='340' side='right'caption='[[2pku]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2pku]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PKU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PKU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2pku FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2pku OCA], [https://pdbe.org/2pku PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2pku RCSB], [https://www.ebi.ac.uk/pdbsum/2pku PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2pku ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PICK1_RAT PICK1_RAT] Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel.<ref>PMID:16138078</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/pk/2pku_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=2pku ConSurf].
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== Publication Abstract from PubMed ==
Protein interacting with c kinase 1 (PICK1) regulates the trafficking of receptors and ion-channels such as AMPA receptors. Traditionally, the PICK1 PDZ domain is regarded as an adaptor capable of binding to receptors trafficked by PICK1, and the lipid-binding BAR domain functions to tether PICK1 directly to membranes. Here, we show that the PICK1 PDZ domain can directly interact with lipid membranes. The PDZ domain and lipid membrane interaction is mediated by both a polybasic amino-acid cluster and a conserved 'Cys-Pro-Cys' motif located away from the peptide ligand-binding groove. Disruption of the PDZ and lipid membrane interaction totally abolished synaptic targeting of PICK1. Although mutation of the CPC motif did not affect the interaction between PICK1 and AMPA receptors, the mutant PICK1 was unable to cluster the GluR2 subunit of the receptor. In neurons, PICK1 containing the same mutation displayed dramatically compromised capacity in the trafficking of AMPA receptors. Taken together, our findings not only uncovered the novel lipid membrane-binding property of the PICK1 PDZ domain, but also provided direct evidence supporting the functional relevance of the PDZ-lipid interaction.

Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes.,Pan L, Wu H, Shen C, Shi Y, Jin W, Xia J, Zhang M EMBO J. 2007 Oct 31;26(21):4576-87. Epub 2007 Oct 4. PMID:17914463<ref>PMID:17914463</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 2pku" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Rattus norvegicus]]
[[Category: Pan L]]
[[Category: Shen C]]
[[Category: Shi Y]]
[[Category: Wu H]]
[[Category: Xia J]]
[[Category: Zhang M]]