3r69

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Revision as of 18:15, 4 August 2016

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

Structural highlights

3r69 is a 2 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	3r68, 2d90
Gene:	Cap70, Nherf3, Pdzk1, Scarb1 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[NHRF3_MOUSE] A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with SLC9A3R1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. May function to connect SCARB1 with the cellular machineries for intracellular cholesterol transport and/or metabolism (By similarity). May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

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-->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-->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-->Ala (PDZ1) + 253Tyr-->Ala (PDZ3)] substitution abrogated all target peptide binding to PDZK1. In vivo hepatic expression of a singly substituted (253Tyr-->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-->Ala (PDZ1) + 253Tyr-->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.

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang S, Yue H, Derin RB, Guggino WB, Li M. Accessory protein facilitated CFTR-CFTR interaction, a molecular mechanism to potentiate the chloride channel activity. Cell. 2000 Sep 29;103(1):169-79. PMID:11051556
↑ Kocher O, Pal R, Roberts M, Cirovic C, Gilchrist A. Targeted disruption of the PDZK1 gene by homologous recombination. Mol Cell Biol. 2003 Feb;23(4):1175-80. PMID:12556478
↑ Gisler SM, Pribanic S, Bacic D, Forrer P, Gantenbein A, Sabourin LA, Tsuji A, Zhao ZS, Manser E, Biber J, Murer H. PDZK1: I. a major scaffolder in brush borders of proximal tubular cells. Kidney Int. 2003 Nov;64(5):1733-45. PMID:14531806 doi:10.1046/j.1523-1755.2003.00266.x
↑ Kato Y, Sai Y, Yoshida K, Watanabe C, Hirata T, Tsuji A. PDZK1 directly regulates the function of organic cation/carnitine transporter OCTN2. Mol Pharmacol. 2005 Mar;67(3):734-43. Epub 2004 Nov 2. PMID:15523054 doi:mol.104.002212
↑ Kocher O, Birrane G, Yesilaltay A, Shechter S, Pal R, Daniels K, Krieger M. 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. J Biol Chem. 2011 May 23. PMID:21602281 doi:10.1074/jbc.M111.242362

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3r69"

@@ Line 1: / Line 1: @@
 ==Molecular analysis of the interaction of the HDL-receptor SR-BI with the PDZ3 domain of its adaptor protein PDZK1==
 <StructureSection load='3r69' size='340' side='right' caption='[[3r69]], [[Resolution|resolution]] 1.50&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3r68|3r68]], [[2d90|2d90]]</td></tr>
 <tr id='gene'><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>
-<tr id='resources'><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>
+<tr id='resources'><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://pdbe.org/3r69 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3r69 RCSB], [http://www.ebi.ac.uk/pdbsum/3r69 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3r69 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 18: / Line 19: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3r69" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

3r69

From Proteopedia

Revision as of 18:15, 4 August 2016

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

Structural highlights

Function

Publication Abstract from PubMed

References

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Proteopedia Page Contributors and Editors (what is this?)

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