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6g52

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Revision as of 06:11, 12 June 2019

CRYSTAL STRUCTURE OF THE CNMP BINDING DOMAIN OF THE MAGNESIUM TRANSPORTER CNNM4

Structural highlights

6g52 is a 9 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Gene:	CNNM4, ACDP4, KIAA1592 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CNNM4_HUMAN] Jalili syndrome. The disease is caused by mutations affecting the gene represented in this entry.

Function

[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.^[1] ^[2]

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^[3]

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

References

↑ Polok B, Escher P, Ambresin A, Chouery E, Bolay S, Meunier I, Nan F, Hamel C, Munier FL, Thilo B, Megarbane A, Schorderet DF. Mutations in CNNM4 cause recessive cone-rod dystrophy with amelogenesis imperfecta. Am J Hum Genet. 2009 Feb;84(2):259-65. doi: 10.1016/j.ajhg.2009.01.006. Epub 2009, Feb 5. PMID:19200527 doi:http://dx.doi.org/10.1016/j.ajhg.2009.01.006
↑ Parry DA, Mighell AJ, El-Sayed W, Shore RC, Jalili IK, Dollfus H, Bloch-Zupan A, Carlos R, Carr IM, Downey LM, Blain KM, Mansfield DC, Shahrabi M, Heidari M, Aref P, Abbasi M, Michaelides M, Moore AT, Kirkham J, Inglehearn CF. Mutations in CNNM4 cause Jalili syndrome, consisting of autosomal-recessive cone-rod dystrophy and amelogenesis imperfecta. Am J Hum Genet. 2009 Feb;84(2):266-73. doi: 10.1016/j.ajhg.2009.01.009. Epub 2009, Feb 5. PMID:19200525 doi:http://dx.doi.org/10.1016/j.ajhg.2009.01.009
↑ 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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6g52"

@@ Line 3: / Line 3: @@
 <StructureSection load='6g52' size='340' side='right'caption='[[6g52]], [[Resolution|resolution]] 3.69&Aring;' 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>
+<table><tr><td colspan='2'>[[6g52]] is a 9 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CNNM4, ACDP4, KIAA1592 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: BLANCO, F J]]
+[[Category: Blanco, F J]]
-[[Category: GIMENEZ, P]]
+[[Category: Gimenez, P]]
-[[Category: HARDY, S]]
+[[Category: Hardy, S]]
-[[Category: MARTINEZ-CRUZ, L A]]
+[[Category: Martinez-Cruz, L A]]
-[[Category: MERINO, N]]
+[[Category: Merino, N]]
-[[Category: MULLER, D]]
+[[Category: Muller, D]]
-[[Category: OYENARTE, I]]
+[[Category: Oyenarte, I]]
-[[Category: SILIQI, D]]
+[[Category: Siliqi, D]]
-[[Category: TREMBLAY, M]]
+[[Category: Tremblay, M]]
-[[Category: ZUBILLAGA, M]]
+[[Category: Zubillaga, M]]
 [[Category: Acdp4]]
 [[Category: Cyclin m4]]

6g52

From Proteopedia

Revision as of 06:11, 12 June 2019

CRYSTAL STRUCTURE OF THE CNMP BINDING DOMAIN OF THE MAGNESIUM TRANSPORTER CNNM4

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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