4e4d - Revision history

OCA at 10:47, 6 November 2024

2024-11-06T10:47:21Z

← Older revision		Revision as of 10:47, 6 November 2024
Line 12:		Line 12:
	== Function ==		== Function ==
	[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.		[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with approximately 500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis approximately 150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.

			RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor.,Nelson CA, Warren JT, Wang MW, Teitelbaum SL, Fremont DH Structure. 2012 Oct 2. pii: S0969-2126(12)00334-6. doi:, 10.1016/j.str.2012.08.030. PMID:23039992<ref>PMID:23039992</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 4e4d" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 17:		Line 26:
	*[[Tumor necrosis factor ligand superfamily 3D structures\|Tumor necrosis factor ligand superfamily 3D structures]]		*[[Tumor necrosis factor ligand superfamily 3D structures\|Tumor necrosis factor ligand superfamily 3D structures]]
	*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]		*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 14:52, 14 March 2024

2024-03-14T14:52:17Z

← Older revision		Revision as of 14:52, 14 March 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4d]] 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=4E4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4D FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4d]] 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=4E4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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]] 2.7Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></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=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [https://pdbe.org/4e4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [https://www.ebi.ac.uk/pdbsum/4e4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4d ProSAT]</span></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=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [https://pdbe.org/4e4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [https://www.ebi.ac.uk/pdbsum/4e4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4d ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.		[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.		[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with approximately 500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis approximately 150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.

	RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor.,Nelson CA, Warren JT, Wang MW, Teitelbaum SL, Fremont DH Structure. 2012 Oct 2. pii: S0969-2126(12)00334-6. doi:, 10.1016/j.str.2012.08.030. PMID:23039992<ref>PMID:23039992</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 4e4d" style="background-color:#fffaf0;"></div>~~

	==See Also==		==See Also==
Line 25:		Line 17:
	*[[Tumor necrosis factor ligand superfamily 3D structures\|Tumor necrosis factor ligand superfamily 3D structures]]		*[[Tumor necrosis factor ligand superfamily 3D structures\|Tumor necrosis factor ligand superfamily 3D structures]]
	*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]		*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:49, 28 September 2022

2022-09-28T06:49:23Z

← Older revision		Revision as of 06:49, 28 September 2022
Line 1:		Line 1:

	==Crystal structure of mouse RANKL-OPG complex==		==Crystal structure of mouse RANKL-OPG complex==
	<StructureSection load='4e4d' size='340' side='right' caption='[[4e4d]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4e4d' size='340' side='right'caption='[[4e4d]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4d]] 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=4E4D OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4E4D FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4d]] 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=4E4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E4D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>~~</td></tr>~~		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3me2\|3me2]], [[3qbq\|3qbq]], [[3alq\|3alq]], [[3k51\|3k51]], [[3qo4\|3qo4]], [[1tnr\|1tnr]]</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=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [https://pdbe.org/4e4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [https://www.ebi.ac.uk/pdbsum/4e4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4d ProSAT]</span></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CD254, ODF, Opgl, Rankl, Tnfsf11, Trance ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Ocif, Opg, Osteoprotegerin, Tnfrsf11b ([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'>[~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [~~http~~://pdbe.org/4e4d PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/4e4d PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4d ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[~~http~~://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.		[[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.
	== Function ==		== Function ==
	[[~~http~~://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. [[http://www.uniprot.org/uniprot/TR11B_MOUSE TR11B_MOUSE]] Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.<ref>PMID:10952716</ref>		[[https://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 22:

	==See Also==		==See Also==
	*[[Tumor necrosis factor receptor\|Tumor necrosis factor receptor]]		*[[Tumor necrosis factor ligand superfamily\|Tumor necrosis factor ligand superfamily]]
			*[[Tumor necrosis factor ligand superfamily 3D structures\|Tumor necrosis factor ligand superfamily 3D structures]]
			*[[Tumor necrosis factor receptor 3D structures\|Tumor necrosis factor receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Lk3 transgenic mice~~]]		[[Category: Large Structures]]
	[[Category: ~~Fremont, D H~~]]		[[Category: Mus musculus]]
	[[Category: ~~Nelson, C A~~]]		[[Category: Fremont DH]]
	[[Category: ~~Cysteine-rich domain]]~~		[[Category: Nelson CA]]
	~~[[Category: Cytokine-signaling protein complex]]~~
	~~[[Category: Jelly-roll fold]]~~
	~~[[Category: Tnf-related activation-induced cytokine-receptor~~]]

OCA at 15:52, 4 August 2016

2016-08-04T15:52:05Z

← Older revision		Revision as of 15:52, 4 August 2016
Line 1:		Line 1:

	==Crystal structure of mouse RANKL-OPG complex==		==Crystal structure of mouse RANKL-OPG complex==
	<StructureSection load='4e4d' size='340' side='right' caption='[[4e4d]], [[Resolution\|resolution]] 2.70Å' scene=''>		<StructureSection load='4e4d' size='340' side='right' caption='[[4e4d]], [[Resolution\|resolution]] 2.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[4e4d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Mus_musculus Mus musculus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4D FirstGlance]. <br>		<table><tr><td colspan='2'>[[4e4d]] 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=4E4D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4D FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3me2\|3me2]], [[3qbq\|3qbq]], [[3alq\|3alq]], [[3k51\|3k51]], [[3qo4\|3qo4]], [[1tnr\|1tnr]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3me2\|3me2]], [[3qbq\|3qbq]], [[3alq\|3alq]], [[3k51\|3k51]], [[3qo4\|3qo4]], [[1tnr\|1tnr]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CD254, ODF, Opgl, Rankl, Tnfsf11, Trance ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 ~~Mus musculus~~]), Ocif, Opg, Osteoprotegerin, Tnfrsf11b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 ~~Mus musculus~~])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CD254, ODF, Opgl, Rankl, Tnfsf11, Trance ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Ocif, Opg, Osteoprotegerin, Tnfrsf11b ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [http://www.ebi.ac.uk/pdbsum/4e4d PDBsum]</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=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [http://pdbe.org/4e4d PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [http://www.ebi.ac.uk/pdbsum/4e4d PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e4d ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
	[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.		[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.		[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy. [[http://www.uniprot.org/uniprot/TR11B_MOUSE TR11B_MOUSE]] Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.<ref>PMID:10952716</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 20:		Line 21:
	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>
	</div>		</div>
			<div class="pdbe-citations 4e4d" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Tumor necrosis factor receptor\|Tumor necrosis factor receptor]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: ~~Mus musculus~~]]		[[Category: Lk3 transgenic mice]]
	[[Category: Fremont, D H]]		[[Category: Fremont, D H]]
	[[Category: Nelson, C A]]		[[Category: Nelson, C A]]

OCA at 10:56, 21 December 2014

2014-12-21T10:56:53Z

← Older revision		Revision as of 10:56, 21 December 2014
Line 1:		Line 1:
	~~{{STRUCTURE_4e4d\| PDB~~=4e4d \| ~~SCENE~~= }}		==Crystal structure of mouse RANKL-OPG complex==
	===~~Crystal~~ structure ~~of mouse RANKL~~-~~OPG complex~~===		<StructureSection load='4e4d' size='340' side='right' caption='[[4e4d]], [[Resolution\|resolution]] 2.70Å' scene=''>
	~~{{ABSTRACT_PUBMED_23039992}}~~		== Structural highlights ==
			<table><tr><td colspan='2'>[[4e4d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E4D FirstGlance]. <br>
	==Disease==		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
			<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3me2\|3me2]], [[3qbq\|3qbq]], [[3alq\|3alq]], [[3k51\|3k51]], [[3qo4\|3qo4]], [[1tnr\|1tnr]]</td></tr>
			<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">CD254, ODF, Opgl, Rankl, Tnfsf11, Trance ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Ocif, Opg, Osteoprotegerin, Tnfrsf11b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=4e4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e4d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4e4d RCSB], [http://www.ebi.ac.uk/pdbsum/4e4d PDBsum]</span></td></tr>
			</table>
			== Disease ==
	[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.		[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.
			== Function ==
			[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Osteoprotegerin (OPG) and receptor activator of nuclear factor kappaB (RANK) are members of the tumor necrosis factor receptor (TNFR) superfamily that regulate osteoclast formation and function by competing for RANK ligand (RANKL). RANKL promotes osteoclast development through RANK activation, while OPG inhibits this process by sequestering RANKL. For comparison, we solved crystal structures of RANKL with RANK and RANKL with OPG. Complementary biochemical and functional studies reveal that the monomeric cytokine-binding region of OPG binds RANKL with approximately 500-fold higher affinity than RANK and inhibits RANKL-stimulated osteoclastogenesis approximately 150 times more effectively, in part because the binding cleft of RANKL makes unique contacts with OPG. Several side chains as well as the C-D and D-E loops of RANKL occupy different orientations when bound to OPG versus RANK. High affinity OPG binding requires a 90s loop Phe residue that is mutated in juvenile Paget's disease. These results suggest cytokine plasticity may help to fine-tune specific tumor necrosis factor (TNF)-family cytokine/receptor pair selectivity.

	~~==Function==~~		RANKL Employs Distinct Binding Modes to Engage RANK and the Osteoprotegerin Decoy Receptor.,Nelson CA, Warren JT, Wang MW, Teitelbaum SL, Fremont DH Structure. 2012 Oct 2. pii: S0969-2126(12)00334-6. doi:, 10.1016/j.str.2012.08.030. PMID:23039992<ref>PMID:23039992</ref>
	~~[[http~~:~~//www~~.~~uniprot~~.~~org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A~~/~~RANK~~. ~~Osteoclast differentiation and activation factor~~. ~~Augments the ability of dendritic cells to stimulate naive T-cell proliferation~~. ~~May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response~~. ~~May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy~~.

	==~~About this Structure~~==		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	~~[[4e4d]] is a 2 chain structure with sequence from [http:~~//~~en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4D OCA].~~		</div>
			== References ==
			<references/>
			__TOC__
			</StructureSection>
	[[Category: Mus musculus]]		[[Category: Mus musculus]]
	[[Category: Fremont, D H.]]		[[Category: Fremont, D H]]
	[[Category: Nelson, C A.]]		[[Category: Nelson, C A]]
	[[Category: Cysteine-rich domain]]		[[Category: Cysteine-rich domain]]
	[[Category: Cytokine-signaling protein complex]]		[[Category: Cytokine-signaling protein complex]]
	[[Category: Jelly-roll fold]]		[[Category: Jelly-roll fold]]
	[[Category: Tnf-related activation-induced cytokine-receptor]]		[[Category: Tnf-related activation-induced cytokine-receptor]]

OCA at 21:47, 24 March 2013

2013-03-24T21:47:45Z

← Older revision		Revision as of 21:47, 24 March 2013
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	~~[[Image:4e4d.png\|left\|200px]]~~

	{{STRUCTURE_4e4d\| PDB=4e4d \| SCENE= }}		{{STRUCTURE_4e4d\| PDB=4e4d \| SCENE= }}
			===Crystal structure of mouse RANKL-OPG complex===
			{{ABSTRACT_PUBMED_23039992}}

	===~~Crystal structure~~ of ~~mouse RANKL~~-~~OPG complex===~~		==Disease==
			[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Note=Deficiency in Tnfsf11 results in failure to form lobulo-alveolar mammary structures during pregnancy, resulting in death of newborns. Trance-deficient mice show severe osteopetrosis, with no osteoclasts, marrow spaces, or tooth eruption, and exhibit profound growth retardation at several skeletal sites, including the limbs, skull, and vertebrae and have marked chondrodysplasia, with thick, irregular growth plates and a relative increase in hypertrophic chondrocytes.

	~~{{ABSTRACT_PUBMED_23039992}}~~		==Function==
			[[http://www.uniprot.org/uniprot/TNF11_MOUSE TNF11_MOUSE]] Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.

	==About this Structure==		==About this Structure==

OCA at 21:31, 12 December 2012

2012-12-12T21:31:44Z

← Older revision		Revision as of 21:31, 12 December 2012
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	[[Image:4e4d.~~jpg~~\|left\|200px]]		[[Image:4e4d.png\|left\|200px]]

	{{STRUCTURE_4e4d\| PDB=4e4d \| SCENE= }}		{{STRUCTURE_4e4d\| PDB=4e4d \| SCENE= }}

OCA at 07:39, 24 October 2012

2012-10-24T07:39:31Z

← Older revision		Revision as of 07:39, 24 October 2012
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	~~'''Unreleased structure'''~~		[[Image:4e4d.jpg\|left\|200px]]

	~~The entry~~ 4e4d ~~is ON HOLD~~ ~~until Paper Publication~~		{{STRUCTURE_4e4d\| PDB=4e4d \| SCENE= }}

	~~Authors: Nelson, C.A., Fremont, D.H.~~		===Crystal structure of mouse RANKL-OPG complex===

	~~Description~~: ~~Crystal structure of mouse RANKL~~-~~OPG~~ complex		{{ABSTRACT_PUBMED_23039992}}

			==About this Structure==
			[[4e4d]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E4D OCA].
			[[Category: Mus musculus]]
			[[Category: Fremont, D H.]]
			[[Category: Nelson, C A.]]
			[[Category: Cysteine-rich domain]]
			[[Category: Cytokine-signaling protein complex]]
			[[Category: Jelly-roll fold]]
			[[Category: Tnf-related activation-induced cytokine-receptor]]

OCA at 06:38, 11 April 2012

2012-04-11T06:38:47Z

← Older revision		Revision as of 06:38, 11 April 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 4e4d is ON HOLD		The entry 4e4d is ON HOLD until Paper Publication

	Authors: Nelson, C.A., Fremont, D.H.		Authors: Nelson, C.A., Fremont, D.H.

	Description: Crystal structure of mouse RANKL-OPG complex		Description: Crystal structure of mouse RANKL-OPG complex

OCA: Protected "4e4d" [edit=sysop:move=sysop]

2012-03-21T07:16:45Z

Protected "4e4d" [edit=sysop:move=sysop]

← Older revision	Revision as of 07:16, 21 March 2012
(No difference)