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3r69

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[[Image:3r69.png|left|200px]]
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==Molecular analysis of the interaction of the HDL-receptor SR-BI with the PDZ3 domain of its adaptor protein PDZK1==
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<StructureSection load='3r69' size='340' side='right' caption='[[3r69]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3r69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3R69 FirstGlance]. <br>
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</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene><br>
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<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r68|3r68]], [[2d90|2d90]]</td></tr>
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<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cap70, Nherf3, Pdzk1, Scarb1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
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<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3r69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3r69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3r69 RCSB], [http://www.ebi.ac.uk/pdbsum/3r69 PDBsum]</span></td></tr>
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<table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The normal expression, cell surface localization and function of the murine HDL receptor SR-BI in hepatocytes in vivo - and thus normal lipoprotein metabolism - depend on its four PDZ domain (PDZ1-PDZ4) containing cytoplasmic adaptor protein PDZK1. Previous studies showed that the C-terminus of SR-BI (target peptide) binds directly to PDZ1 and influences hepatic SR-BI protein expression. Unexpectedly an inactivating mutation in PDZ1 (20Tyr--&gt;Ala) only partially, rather than completely, suppresses PDZK1's ability to control hepatic SR-BI. We used isothermal titration calorimetry to show that PDZ3, but not PDZ2 or PDZ4, can also bind the target peptide (Kd= 37.0 muM), albeit with ~10-fold lower affinity than PDZ1. This binding is abrogated by a 253Tyr--&gt;Ala substitution. Comparison of the 1.5 A resolution crystal structure of PDZ3 with its bound target peptide (505QEAKL509) to that of peptide-bound PDZ1 indicated fewer target peptide stabilizing atomic interactions (hydrogen bonds and hydrophobic interactions) in PDZ3. A double [20Tyr--&gt;Ala (PDZ1) + 253Tyr--&gt;Ala (PDZ3)] substitution abrogated all target peptide binding to PDZK1. In vivo hepatic expression of a singly substituted (253Tyr--&gt;Ala (PDZ3)) PDZK1 transgene (Tg) was able to correct all of the SR-BI-related defects in PDZK1 KO mice, whereas the doubly substituted [20Tyr--&gt;Ala (PDZ1) + 253Tyr--&gt;Ala (PDZ3)]-Tg was unable to correct these defects. Thus, we conclude that PDZK1-mediated control of hepatic SR-BI requires direct binding of SR-BI's C-terminus to either the PDZ1 or PDZ3 domain, and that binding to both domains simultaneously is not required for PDZK1 control of hepatic SR-BI.
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Identification of the PDZ3 domain of the adaptor protein PDZK1 as a second, physiologically functional, binding site for the C-terminus of the HDL receptor SR-BI.,Kocher O, Birrane G, Yesilaltay A, Shechter S, Pal R, Daniels K, Krieger M J Biol Chem. 2011 May 23. PMID:21602281<ref>PMID:21602281</ref>
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The line below this paragraph, containing "STRUCTURE_3r69", creates the "Structure Box" on the page.
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{{STRUCTURE_3r69| PDB=3r69 | SCENE= }}
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===Molecular analysis of the interaction of the HDL-receptor SR-BI with the PDZ3 domain of its adaptor protein PDZK1===
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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</div>
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== References ==
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<references/>
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The line below this paragraph, {{ABSTRACT_PUBMED_21602281}}, adds the Publication Abstract to the page
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__TOC__
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(as it appears on PubMed at http://www.pubmed.gov), where 21602281 is the PubMed ID number.
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</StructureSection>
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[[Category: Lk3 transgenic mice]]
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{{ABSTRACT_PUBMED_21602281}}
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==About this Structure==
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[[3r69]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus,_mus_musculus Mus musculus, mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3R69 OCA].
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==Reference==
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<ref group="xtra">PMID:021602281</ref><references group="xtra"/>
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[[Category: Mus musculus, mus musculus]]
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[[Category: Birrane, G.]]
[[Category: Birrane, G.]]
[[Category: Kocher, O.]]
[[Category: Kocher, O.]]

Revision as of 04:50, 5 June 2014

Molecular analysis of the interaction of the HDL-receptor SR-BI with the PDZ3 domain of its adaptor protein PDZK1

3r69, resolution 1.50Å

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