5tsr: Difference between revisions
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==Crystal structure of PRL-3 phosphatase in complex with the Bateman domain of CNNM3 magnesium transporter== | ==Crystal structure of PRL-3 phosphatase in complex with the Bateman domain of CNNM3 magnesium transporter== | ||
<StructureSection load='5tsr' size='340' side='right' caption='[[5tsr]], [[Resolution|resolution]] 3.19Å' scene=''> | <StructureSection load='5tsr' size='340' side='right'caption='[[5tsr]], [[Resolution|resolution]] 3.19Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5tsr]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TSR OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[5tsr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5TSR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5TSR FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.188Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5tsr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5tsr OCA], [https://pdbe.org/5tsr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5tsr RCSB], [https://www.ebi.ac.uk/pdbsum/5tsr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5tsr ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/TP4A3_HUMAN TP4A3_HUMAN] Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.<ref>PMID:11355880</ref> <ref>PMID:12782572</ref> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The phosphatases of regenerating liver (PRLs) are involved in tumorigenesis and metastatic cancer yet their cellular function remains unclear. Recent reports have shown PRL phosphatases bind tightly to the CNNM family of membrane proteins to regulate magnesium efflux. Here, we characterize the interactions between the CBS-pair (Bateman) domain of CNNM3 and either PRL2 or PRL3 using X-ray crystallography, isothermal titration calorimetry, and activity assays. We report four new crystal structures of PRL proteins bound to the CNNM3 CBS-pair domain that reveal the effects of cysteine disulphide formation and nucleotide binding on complex formation. We use comprehensive mutagenesis of the PRL3 catalytic site to quantify the importance of different PRL amino acids, including cysteine 104, leucine 108, and arginine 110, for CNNM binding and phosphatase activity. We show the PRL3 R138E mutant is selectively deficient in CNNM3 binding with the potential to distinguish between the downstream effects of phosphatase and CNNM-binding activities in vivo. Through a novel activity assay, we show that PRL3 has magnesium-sensitive phosphatase activity with ATP and other nucleotides. Our results identify a strong correlation between phosphatase activity and CNNM binding and support the contention that PRL function as pseudophosphatases regulated by chemical modifications of their catalytic cysteine. | |||
PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3.,Zhang H, Kozlov G, Li X, Wu H, Gulerez I, Gehring K Sci Rep. 2017 Mar 3;7(1):48. doi: 10.1038/s41598-017-00147-2. PMID:28246390<ref>PMID:28246390</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 5tsr" 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: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Gehring K]] | ||
[[Category: | [[Category: Kozlov G]] | ||
[[Category: | [[Category: Zhang H]] | ||
Latest revision as of 16:10, 4 October 2023
Crystal structure of PRL-3 phosphatase in complex with the Bateman domain of CNNM3 magnesium transporterCrystal structure of PRL-3 phosphatase in complex with the Bateman domain of CNNM3 magnesium transporter
Structural highlights
FunctionTP4A3_HUMAN Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.[1] [2] Publication Abstract from PubMedThe phosphatases of regenerating liver (PRLs) are involved in tumorigenesis and metastatic cancer yet their cellular function remains unclear. Recent reports have shown PRL phosphatases bind tightly to the CNNM family of membrane proteins to regulate magnesium efflux. Here, we characterize the interactions between the CBS-pair (Bateman) domain of CNNM3 and either PRL2 or PRL3 using X-ray crystallography, isothermal titration calorimetry, and activity assays. We report four new crystal structures of PRL proteins bound to the CNNM3 CBS-pair domain that reveal the effects of cysteine disulphide formation and nucleotide binding on complex formation. We use comprehensive mutagenesis of the PRL3 catalytic site to quantify the importance of different PRL amino acids, including cysteine 104, leucine 108, and arginine 110, for CNNM binding and phosphatase activity. We show the PRL3 R138E mutant is selectively deficient in CNNM3 binding with the potential to distinguish between the downstream effects of phosphatase and CNNM-binding activities in vivo. Through a novel activity assay, we show that PRL3 has magnesium-sensitive phosphatase activity with ATP and other nucleotides. Our results identify a strong correlation between phosphatase activity and CNNM binding and support the contention that PRL function as pseudophosphatases regulated by chemical modifications of their catalytic cysteine. PRL3 phosphatase active site is required for binding the putative magnesium transporter CNNM3.,Zhang H, Kozlov G, Li X, Wu H, Gulerez I, Gehring K Sci Rep. 2017 Mar 3;7(1):48. doi: 10.1038/s41598-017-00147-2. PMID:28246390[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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