6g52
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==CRYSTAL STRUCTURE OF THE CNMP BINDING DOMAIN OF THE MAGNESIUM TRANSPORTER CNNM4== | |
| + | <StructureSection load='6g52' size='340' side='right'caption='[[6g52]], [[Resolution|resolution]] 3.69Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6g52]] is a 9 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G52 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G52 FirstGlance]. <br> | ||
| + | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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=6g52 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g52 OCA], [http://pdbe.org/6g52 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g52 RCSB], [http://www.ebi.ac.uk/pdbsum/6g52 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g52 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/CNNM4_HUMAN CNNM4_HUMAN]] Jalili syndrome. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/CNNM4_HUMAN CNNM4_HUMAN]] Probable metal transporter. The interaction with the metal ion chaperone COX11 suggests that it may play a role in sensory neuron functions (By similarity). May play a role in biomineralization and retinal function.<ref>PMID:19200527</ref> <ref>PMID:19200525</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Phosphatases of regenerating liver (PRLs), the most oncogenic of all protein tyrosine phosphatases (PTPs), play a critical role in metastatic progression of cancers. Recent findings established a new paradigm by uncovering that their association with magnesium transporters of the Cyclin M (CNNM) family causes intracellular magnesium levels that promotes oncogenic transformation. On the other hand, it has recently been highlighted essential roles of the CNNM family in regulation of the circadian rhythm, and reproduction. Here, we describe the crystal structure of PRL-1 in complex with the Bateman module of CNNM2 (CNNM2BAT), which consists of two cystathionine beta-synthase (CBS) domains (IPR000664) and represents an intracellular regulatory module of the transporter. The structure reveals a heterotetrameric association, consisting of a disc-like homodimer of CNNM2BAT bound to two independent PRL-1 molecules, each one located at opposite tips of the disc. The structure highlights the key role played by residue D558 at the extended loop of the CBS2 motif of CNNM2 in maintaining the association between the two proteins and proves that the interaction between CNNM2 and PRL-1 occurs via the catalytic domain of the phosphatase. Our data shed new light on the structural basis underlying the interaction between PRL phosphatases and CNNM transporters and provides a hypothesis about the molecular mechanism by which PRL-1, upon binding to CNNM2, might increase the intracellular concentration of Mg2+ thereby contributing to tumor progression and metastasis. The availability of this structure sets the basis for the rational design of compounds modulating PRL-1 and CNNM2 activities. | ||
| - | + | Structural Basis of the Oncogenic Interaction of Phosphatase PRL-1 with the Magnesium Transporter CNNM2.,Gimenez-Mascarell P, Oyenarte I, Hardy S, Breiderhoff T, Stuiver M, Kostantin E, Diercks T, Pey AL, Ereno-Orbea J, Martinez-Chantar ML, Khalaf-Nazzal R, Claverie-Martin F, Muller D, Tremblay ML, Martinez-Cruz LA J Biol Chem. 2016 Nov 29. pii: jbc.M116.759944. PMID:27899452<ref>PMID:27899452</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6g52" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: BLANCO, F J]] | ||
| + | [[Category: GIMENEZ, P]] | ||
| + | [[Category: HARDY, S]] | ||
| + | [[Category: MARTINEZ-CRUZ, L A]] | ||
| + | [[Category: MERINO, N]] | ||
| + | [[Category: MULLER, D]] | ||
| + | [[Category: OYENARTE, I]] | ||
| + | [[Category: SILIQI, D]] | ||
| + | [[Category: TREMBLAY, M]] | ||
| + | [[Category: ZUBILLAGA, M]] | ||
| + | [[Category: Acdp4]] | ||
| + | [[Category: Cyclin m4]] | ||
| + | [[Category: Jalili syndrome]] | ||
| + | [[Category: Magnesium]] | ||
| + | [[Category: Magnesium absorption]] | ||
| + | [[Category: Magnesium homeostasis]] | ||
| + | [[Category: Metal transport]] | ||
| + | [[Category: Transporter]] | ||
Revision as of 07:17, 10 April 2019
CRYSTAL STRUCTURE OF THE CNMP BINDING DOMAIN OF THE MAGNESIUM TRANSPORTER CNNM4
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