4f8k

From Proteopedia

(Difference between revisions)

Revision as of 19:03, 25 December 2014

Molecular analysis of the interaction between the prostacyclin receptor and the first PDZ domain of PDZK1

Structural highlights

4f8k is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3ngh
Gene:	Cap70, Nherf3, Pdzk1, Prostacyclin receptor, Ptgir (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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 prostanoid prostacyclin, or prostaglandin I, plays an essential role in many aspects of cardiovascular disease. The actions of prostacyclin are mainly mediated through its activation of the prostacyclin receptor or, in short, the IP. In recent studies, the cytoplasmic carboxy-terminal domain of the IP was shown to bind several PDZ domains of the multi-PDZ adaptor PDZK1. The interaction between the two proteins was found to enhance cell surface expression of the IP and to be functionally important in promoting prostacyclin-induced endothelial cell migration and angiogenesis. To investigate the interaction of the IP with the first PDZ domain (PDZ1) of PDZK1, we generated a nine residue peptide (KKIAACSLC) containing the seven carboxy-terminal amino acids of the IP and measured its binding affinity to a recombinant protein corresponding to PDZ1 by isothermal titration calorimetry. We determined that the IP interacts with PDZ1 with a binding affinity of 8.2 microM. Using the same technique, we also determined that the farnesylated form of carboxy-terminus of the IP does not bind to PDZ1. To understand the molecular basis of these findings, we solved the high resolution crystal structure of PDZ1 bound to a 7-residue peptide derived from the carboxy-terminus of the non-farnesylated form of IP (IAACSLC). Analysis of the structure demonstrates a critical role for the three carboxy-terminal amino acids in establishing a strong interaction with PDZ1 and explains the inability of the farnesylated form of IP to interact with the PDZ1 domain of PDZK1 at least .

Molecular Analysis of the Prostacyclin Receptor's Interaction with the PDZ1 Domain of Its Adaptor Protein PDZK1.,Birrane G, Mulvaney EP, Pal R, Kinsella BT, Kocher O PLoS One. 2013;8(2):e53819. doi: 10.1371/journal.pone.0053819. Epub 2013 Feb 6. PMID:23457445^[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
↑ Birrane G, Mulvaney EP, Pal R, Kinsella BT, Kocher O. Molecular Analysis of the Prostacyclin Receptor's Interaction with the PDZ1 Domain of Its Adaptor Protein PDZK1. PLoS One. 2013;8(2):e53819. doi: 10.1371/journal.pone.0053819. Epub 2013 Feb 6. PMID:23457445 doi:http://dx.doi.org/10.1371/journal.pone.0053819

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/4f8k"

@@ Line 7: / Line 7: @@
 <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=4f8k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4f8k OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4f8k RCSB], [http://www.ebi.ac.uk/pdbsum/4f8k PDBsum]</span></td></tr>
 </table>
+== Function ==
+[[http://www.uniprot.org/uniprot/NHRF3_MOUSE 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.<ref>PMID:11051556</ref> <ref>PMID:12556478</ref> <ref>PMID:14531806</ref> <ref>PMID:15523054</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==

4f8k

From Proteopedia

Revision as of 19:03, 25 December 2014

Molecular analysis of the interaction between the prostacyclin receptor and the first PDZ domain of PDZK1

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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