4e4d

From Proteopedia

(Difference between revisions)

Revision as of 06:49, 28 September 2022

Crystal structure of mouse RANKL-OPG complex

Structural highlights

4e4d is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.

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^[1]

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

References

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

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4e4d"

Categories: Large Structures | Mus musculus | Fremont DH | Nelson CA

@@ Line 1: / Line 1: @@
 ==Crystal structure of mouse RANKL-OPG complex==
-<StructureSection load='4e4d' size='340' side='right' caption='[[4e4d]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
+<StructureSection load='4e4d' size='340' side='right'caption='[[4e4d]], [[Resolution|resolution]] 2.70&Aring;' scene=''>
 == 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>
 == 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 ==
-[[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;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 22: @@
 ==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/>
 __TOC__
 </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]]

4e4d

From Proteopedia

Revision as of 06:49, 28 September 2022

Crystal structure of mouse RANKL-OPG complex

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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