6g52 - Revision history

OCA at 12:55, 25 December 2019

2019-12-25T12:55:05Z

←Older revision		Revision as of 12:55, 25 December 2019
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	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== 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~~.	+	The four member family of "Cyclin and Cystathionine beta-synthase (CBS) domain divalent metal cation transport mediators", CNNMs, are the least-studied mammalian magnesium transport mediators. CNNM4 is abundant in the brain and the intestinal tract, and its abnormal activity causes Jalili Syndrome. Recent findings show that suppression of CNNM4 in mice promotes malignant progression of intestinal polyps and is linked to infertility. The association of CNNM4 with phosphatases of the regenerating liver, PRLs, abrogates its Mg(2+)-efflux capacity, thus resulting in an increased intracellular Mg(2+) concentration that favors tumor growth. Here we present the crystal structures of the two independent intracellular domains of human CNNM4, i.e., the Bateman module and the cyclic nucleotide binding-like domain (cNMP). We also derive a model structure for the full intracellular region in the absence and presence of MgATP and the oncogenic interacting partner, PRL-1. We find that only the Bateman module interacts with ATP and Mg(2+), at non-overlapping sites facilitating their positive cooperativity. Furthermore, both domains dimerize autonomously, where the cNMP domain dimer forms a rigid cleft to restrict the Mg(2+) induced sliding of the inserting CBS1 motives of the Bateman module, from a twisted to a flat disk shaped dimer.

-	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>	+	Structural Insights into the Intracellular Region of the Human Magnesium Transport Mediator CNNM4.,Gimenez-Mascarell P, Oyenarte I, Gonzalez-Recio I, Fernandez-Rodriguez C, Corral-Rodriguez MA, Campos-Zarraga I, Simon J, Kostantin E, Hardy S, Diaz Quintana A, Zubillaga Lizeaga M, Merino N, Diercks T, Blanco FJ, Diaz Moreno I, Martinez-Chantar ML, Tremblay ML, Muller D, Siliqi D, Martinez-Cruz LA Int J Mol Sci. 2019 Dec 12;20(24). pii: ijms20246279. doi: 10.3390/ijms20246279. PMID:31842432<ref>PMID:31842432</ref>

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

OCA at 06:11, 12 June 2019

2019-06-12T06:11:36Z

←Older revision		Revision as of 06:11, 12 June 2019
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	<StructureSection load='6g52' size='340' side='right'caption='[[6g52]], [[Resolution\|resolution]] 3.69Å' scene=''>		<StructureSection load='6g52' size='340' side='right'caption='[[6g52]], [[Resolution\|resolution]] 3.69Å' scene=''>
	== Structural highlights ==		== 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>		</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>		<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>		</table>
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Large Structures]]		[[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: Acdp4]]
	[[Category: Cyclin m4]]		[[Category: Cyclin m4]]

OCA at 07:17, 10 April 2019

2019-04-10T07:17:34Z

←Older revision		Revision as of 07:17, 10 April 2019
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-	'''Unreleased structure'''

-	~~The entry~~ 6g52 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==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.

-	~~Authors~~:	+	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>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</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]]

OCA at 04:24, 18 April 2018

2018-04-18T04:24:46Z

←Older revision		Revision as of 04:24, 18 April 2018
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6g52 is ON HOLD	+	The entry 6g52 is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6g52" [edit=sysop:move=sysop]

2018-04-04T04:54:10Z

Protected "6g52" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:54, 4 April 2018

OCA: New page: '''Unreleased structure''' The entry 6g52 is ON HOLD Authors: Description: Category: Unreleased Structures

2018-04-04T04:54:08Z

New page: '''Unreleased structure''' The entry 6g52 is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6g52 is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]