|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Structure of PRL-1 in complex with the Bateman domain of CNNM2== | | ==Structure of PRL-1 in complex with the Bateman domain of CNNM2== |
| - | <StructureSection load='5mmz' size='340' side='right' caption='[[5mmz]], [[Resolution|resolution]] 2.40Å' scene=''> | + | <StructureSection load='5mmz' size='340' side='right'caption='[[5mmz]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mmz]] 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=5MMZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MMZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mmz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MMZ FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5lxq|5lxq]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cnnm2, Acdp2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Ptp4a1, Prl1 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5mmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mmz OCA], [https://pdbe.org/5mmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mmz RCSB], [https://www.ebi.ac.uk/pdbsum/5mmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mmz ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-tyrosine-phosphatase Protein-tyrosine-phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.48 3.1.3.48] </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=5mmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mmz OCA], [http://pdbe.org/5mmz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mmz RCSB], [http://www.ebi.ac.uk/pdbsum/5mmz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mmz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CNNM2_MOUSE CNNM2_MOUSE]] Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+).<ref>PMID:15899945</ref> [[http://www.uniprot.org/uniprot/TP4A1_MOUSE TP4A1_MOUSE]] Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. May play a role in the development and maintenance of differentiating epithelial tissues (By similarity). | + | [https://www.uniprot.org/uniprot/CNNM2_MOUSE CNNM2_MOUSE] Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+).<ref>PMID:15899945</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 20: |
Line 18: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5mmz" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5mmz" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Dual specificity phosphatase 3D structures|Dual specificity phosphatase 3D structures]] |
| | + | *[[Tyrosine phosphatase 3D structures|Tyrosine phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Protein-tyrosine-phosphatase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Breiderhoff, T]] | + | [[Category: Breiderhoff T]] |
| - | [[Category: Claverie-Martin, F]] | + | [[Category: Claverie-Martin F]] |
| - | [[Category: Diercks, T]] | + | [[Category: Diercks T]] |
| - | [[Category: Ereno-Orbea, J]] | + | [[Category: Ereno-Orbea J]] |
| - | [[Category: Gimenez-Mascarell, P]] | + | [[Category: Gimenez-Mascarell P]] |
| - | [[Category: Hardy, S]] | + | [[Category: Hardy S]] |
| - | [[Category: Khalaf-Nazzal, R]] | + | [[Category: Khalaf-Nazzal R]] |
| - | [[Category: Kostantin, E]] | + | [[Category: Kostantin E]] |
| - | [[Category: Martinez-Chantar, M L]] | + | [[Category: Martinez-Chantar ML]] |
| - | [[Category: Martinez-Cruz, L A]] | + | [[Category: Martinez-Cruz LA]] |
| - | [[Category: Muller, D]] | + | [[Category: Muller D]] |
| - | [[Category: Oyenarte, I]] | + | [[Category: Oyenarte I]] |
| - | [[Category: Pey, A L]] | + | [[Category: Pey AL]] |
| - | [[Category: Stuiver, M]] | + | [[Category: Stuiver M]] |
| - | [[Category: Tremblay, M L]] | + | [[Category: Tremblay ML]] |
| - | [[Category: Acdp]]
| + | |
| - | [[Category: Cyclin m]]
| + | |
| - | [[Category: Magnesium transport]]
| + | |
| - | [[Category: Metal transport]]
| + | |
| Structural highlights
Function
CNNM2_MOUSE Divalent metal cation transporter. Mediates transport of divalent metal cations in an order of Mg(2+) > Co(2+) > Mn(2+) > Sr(2+) > Ba(2+) > Cu(2+) > Fe(2+).[1]
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Goytain A, Quamme GA. Functional characterization of ACDP2 (ancient conserved domain protein), a divalent metal transporter. Physiol Genomics. 2005 Aug 11;22(3):382-9. Epub 2005 May 17. PMID:15899945 doi:http://dx.doi.org/10.1152/physiolgenomics.00058.2005
- ↑ 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. Structural Basis of the Oncogenic Interaction of Phosphatase PRL-1 with the Magnesium Transporter CNNM2. J Biol Chem. 2016 Nov 29. pii: jbc.M116.759944. PMID:27899452 doi:http://dx.doi.org/10.1074/jbc.M116.759944
|
