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| | ==TRIMCyp cyclophilin domain from Macaca mulatta: H70C mutant, HIV-1 CA(O-loop) complex== | | ==TRIMCyp cyclophilin domain from Macaca mulatta: H70C mutant, HIV-1 CA(O-loop) complex== |
| - | <StructureSection load='4dge' size='340' side='right' caption='[[4dge]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4dge' size='340' side='right'caption='[[4dge]], [[Resolution|resolution]] 2.20Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4dge]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/9hiv1 9hiv1] and [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DGE OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DGE FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4dge]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DGE FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4dga|4dga]], [[4dgb|4dgb]], [[4dgc|4dgc]], [[4dgd|4dgd]]</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]] 2.2Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TRIMCyp ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9544 MACMU]), gag ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11676 9HIV1])</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=4dge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dge OCA], [https://pdbe.org/4dge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dge RCSB], [https://www.ebi.ac.uk/pdbsum/4dge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dge ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Peptidylprolyl_isomerase Peptidylprolyl isomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.2.1.8 5.2.1.8] </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=4dge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dge OCA], [http://pdbe.org/4dge PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4dge RCSB], [http://www.ebi.ac.uk/pdbsum/4dge PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4dge ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q72497_9HIV1 Q72497_9HIV1]] Capsid protein p24 forms the conical core of the virus that encapsulates the genomic RNA-nucleocapsid complex (By similarity). Nucleocapsid protein p7 encapsulates and protects viral dimeric unspliced (genomic) RNA. Binds these RNAs through its zinc fingers (By similarity).[SAAS:SAAS012344_004_011858] | + | [https://www.uniprot.org/uniprot/PPIA_MACMU PPIA_MACMU] Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (By similarity). Activates endothelial cells (ECs) in a proinflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (By similarity). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (By similarity). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (By similarity). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (By similarity). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (By similarity).[UniProtKB:P17742][UniProtKB:P62937] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Cyclophilin|Cyclophilin]] | + | *[[Cyclophilin 3D structures|Cyclophilin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Macmu]] | + | [[Category: Human immunodeficiency virus 1]] |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Bichel, K]] | + | [[Category: Macaca mulatta]] |
| - | [[Category: Caines, M E.C]] | + | [[Category: Bichel K]] |
| - | [[Category: James, L C]] | + | [[Category: Caines MEC]] |
| - | [[Category: McEwan, W A]] | + | [[Category: James LC]] |
| - | [[Category: Price, A J]] | + | [[Category: McEwan WA]] |
| - | [[Category: Anti-viral protein]] | + | [[Category: Price AJ]] |
| - | [[Category: Isomerase-viral protein complex]]
| + | |
| Structural highlights
Function
PPIA_MACMU Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (By similarity). Activates endothelial cells (ECs) in a proinflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (By similarity). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (By similarity). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (By similarity). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (By similarity). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (By similarity).[UniProtKB:P17742][UniProtKB:P62937]
Publication Abstract from PubMed
Rhesus macaque TRIMCyp (RhTC) is a potent primate antiviral host protein that inhibits the replication of diverse HIV viruses. Here we show that it has acquired the ability to target multiple viruses by evolving an active site that interconverts between multiple conformations. Mutations that have relieved active site constraints allow RhTC to dynamically sample conformational space, including radically different conformers that target both HIV-1 and HIV-2 viruses. Introduction of a reversible constraint into RhTC allows specificity to be switched between a single conformation specific for HIV-1 and a dynamic ensemble that targets multiple viruses. These results show that conformational diversity can be used to expand the target diversity of innate immune receptors by supplementing their limited genetic variability with variability in protein structure.
Diverse HIV viruses are targeted by a conformationally dynamic antiviral.,Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC Nat Struct Mol Biol. 2012 Mar 11. doi: 10.1038/nsmb.2253. PMID:22407016[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC. Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nat Struct Mol Biol. 2012 Mar 11. doi: 10.1038/nsmb.2253. PMID:22407016 doi:10.1038/nsmb.2253
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