2n83

From Proteopedia

(Difference between revisions)

Revision as of 15:41, 8 June 2021

p75NTR DD:RIP2 CARD

Structural highlights

2n83 is a 2 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	2n7z, 2n80, 2n97
Gene:	NGFR, TNFRSF16 (HUMAN), RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TNR16_HUMAN] Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells.^[1] [RIPK2_HUMAN] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.^[2] ^[3] ^[4] ^[5]

Publication Abstract from PubMed

Death domains (DDs) mediate assembly of oligomeric complexes for activation of downstream signaling pathways through incompletely understood mechanisms. Here we report structures of complexes formed by the DD of p75 neurotrophin receptor (p75NTR) with RhoGDI, for activation of the RhoA pathway, with caspase recruitment domain (CARD) of RIP2 kinase, for activation of the NF-kB pathway, and with itself, revealing how DD dimerization controls access of intracellular effectors to the receptor. RIP2 CARD and RhoGDI bind to p75NTR DD at partially overlapping epitopes with over 100-fold difference in affinity, revealing the mechanism by which RIP2 recruitment displaces RhoGDI upon ligand binding. The p75NTR DD forms non-covalent, low-affinity symmetric dimers in solution. The dimer interface overlaps with RIP2 CARD but not RhoGDI binding sites, supporting a model of receptor activation triggered by separation of DDs. These structures reveal how competitive protein-protein interactions orchestrate the hierarchical activation of downstream pathways in non-catalytic receptors.

Structural basis of death domain signaling in the p75 neurotrophin receptor.,Lin Z, Tann JY, Goh ET, Kelly C, Lim KB, Gao JF, Ibanez CF Elife. 2015 Dec 8;4. pii: e11692. doi: 10.7554/eLife.11692. PMID:26646181^[6]

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

References

↑ Mi S, Lee X, Shao Z, Thill G, Ji B, Relton J, Levesque M, Allaire N, Perrin S, Sands B, Crowell T, Cate RL, McCoy JM, Pepinsky RB. LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex. Nat Neurosci. 2004 Mar;7(3):221-8. Epub 2004 Feb 15. PMID:14966521 doi:http://dx.doi.org/10.1038/nn1188
↑ Ruefli-Brasse AA, Lee WP, Hurst S, Dixit VM. Rip2 participates in Bcl10 signaling and T-cell receptor-mediated NF-kappaB activation. J Biol Chem. 2004 Jan 9;279(2):1570-4. Epub 2003 Nov 24. PMID:14638696 doi:http://dx.doi.org/10.1074/jbc.C300460200
↑ Manon F, Favier A, Nunez G, Simorre JP, Cusack S. Solution structure of NOD1 CARD and mutational analysis of its interaction with the CARD of downstream kinase RICK. J Mol Biol. 2007 Jan 5;365(1):160-74. Epub 2006 Sep 29. PMID:17054981 doi:10.1016/j.jmb.2006.09.067
↑ Hasegawa M, Fujimoto Y, Lucas PC, Nakano H, Fukase K, Nunez G, Inohara N. A critical role of RICK/RIP2 polyubiquitination in Nod-induced NF-kappaB activation. EMBO J. 2008 Jan 23;27(2):373-83. Epub 2007 Dec 13. PMID:18079694 doi:http://dx.doi.org/10.1038/sj.emboj.7601962
↑ Tigno-Aranjuez JT, Asara JM, Abbott DW. Inhibition of RIP2's tyrosine kinase activity limits NOD2-driven cytokine responses. Genes Dev. 2010 Dec 1;24(23):2666-77. doi: 10.1101/gad.1964410. PMID:21123652 doi:http://dx.doi.org/10.1101/gad.1964410
↑ Lin Z, Tann JY, Goh ET, Kelly C, Lim KB, Gao JF, Ibanez CF. Structural basis of death domain signaling in the p75 neurotrophin receptor. Elife. 2015 Dec 8;4. pii: e11692. doi: 10.7554/eLife.11692. PMID:26646181 doi:http://dx.doi.org/10.7554/eLife.11692

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2n83"

@@ Line 1: / Line 1: @@
 ==p75NTR DD:RIP2 CARD==
-<StructureSection load='2n83' size='340' side='right' caption='[[2n83]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='2n83' size='340' side='right'caption='[[2n83]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2n83]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N83 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2N83 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2n83]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N83 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N83 FirstGlance]. <br>
-</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2n7z|2n7z]], [[2n80|2n80]], [[2n97|2n97]]</td></tr>
+</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2n7z|2n7z]], [[2n80|2n80]], [[2n97|2n97]]</div></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NGFR, TNFRSF16 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NGFR, TNFRSF16 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 ([https://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=2n83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n83 OCA], [http://pdbe.org/2n83 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2n83 RCSB], [http://www.ebi.ac.uk/pdbsum/2n83 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2n83 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=2n83 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n83 OCA], [https://pdbe.org/2n83 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n83 RCSB], [https://www.ebi.ac.uk/pdbsum/2n83 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n83 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/TNR16_HUMAN TNR16_HUMAN]] Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells.<ref>PMID:14966521</ref>  [[http://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN]] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>
+[[https://www.uniprot.org/uniprot/TNR16_HUMAN TNR16_HUMAN]] Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Low affinity receptor which can bind to NGF, BDNF, NT-3, and NT-4. Can mediate cell survival as well as cell death of neural cells.<ref>PMID:14966521</ref>  [[https://www.uniprot.org/uniprot/RIPK2_HUMAN RIPK2_HUMAN]] Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains. Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases BIRC2 and BIRC3. The polyubiquitinated protein mediates the recruitment of MAP3K7/TAK1 to IKBKG/NEMO and induces 'Lys-63'-linked polyubiquitination of IKBKG/NEMO and subsequent activation of IKBKB/IKKB. In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis. Plays also a role during engagement of the T-cell receptor (TCR) in promoting BCL10 phosphorylation and subsequent NF-kappa-B activation.<ref>PMID:14638696</ref> <ref>PMID:17054981</ref> <ref>PMID:18079694</ref> <ref>PMID:21123652</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 21: / Line 21: @@
 ==See Also==
-*[[Tumor necrosis factor receptor|Tumor necrosis factor receptor]]
+*[[Tumor necrosis factor receptor 3D structures|Tumor necrosis factor receptor 3D structures]]
 == References ==
 <references/>
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Ibanez, C F]]
 [[Category: Lin, Z]]

2n83

From Proteopedia

Revision as of 15:41, 8 June 2021

p75NTR DD:RIP2 CARD

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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