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| | <StructureSection load='2wlw' size='340' side='right'caption='[[2wlw]], [[Resolution|resolution]] 1.50Å' scene=''> | | <StructureSection load='2wlw' size='340' side='right'caption='[[2wlw]], [[Resolution|resolution]] 1.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2wlw]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Macmu Macmu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WLW OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2WLW FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2wlw]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WLW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WLW FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wlv|2wlv]]</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]] 1.5Å</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'>[https://proteopedia.org/fgij/fg.htm?mol=2wlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wlw OCA], [https://pdbe.org/2wlw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wlw RCSB], [https://www.ebi.ac.uk/pdbsum/2wlw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wlw ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2wlw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wlw OCA], [http://pdbe.org/2wlw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2wlw RCSB], [http://www.ebi.ac.uk/pdbsum/2wlw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2wlw ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/B1P761_MACMU B1P761_MACMU]] PPIases accelerate the folding of proteins (By similarity).[RuleBase:RU000493] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). | + | [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] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Macmu]] | + | [[Category: Macaca mulatta]] |
| - | [[Category: Peptidylprolyl isomerase]]
| + | [[Category: James LC]] |
| - | [[Category: James, L C]] | + | [[Category: Lammers M]] |
| - | [[Category: Lammers, M]] | + | [[Category: Marzetta F]] |
| - | [[Category: Marzetta, F]] | + | [[Category: Price AJ]] |
| - | [[Category: Price, A J]] | + | [[Category: Schaller T]] |
| - | [[Category: Schaller, T]] | + | [[Category: Towers GJ]] |
| - | [[Category: Towers, G J]] | + | [[Category: Wilson SJ]] |
| - | [[Category: Wilson, S J]] | + | [[Category: Ylinen LMJ]] |
| - | [[Category: Ylinen, L M.J]] | + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Rhesus macaque trim-cyp]]
| + | |
| - | [[Category: Rotamase]]
| + | |
| 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]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
TRIMCyps are primate antiretroviral proteins that potently inhibit HIV replication. Here we describe how rhesus macaque TRIMCyp (RhTC) has evolved to target and restrict HIV-2. We show that the ancestral cyclophilin A (CypA) domain of RhTC targets HIV-2 capsid with weak affinity, which is strongly increased in RhTC by two mutations (D66N and R69H) at the expense of HIV-1 binding. These mutations disrupt a constraining intramolecular interaction in CypA, triggering the complete restructuring (>16 A) of an active site loop. This new configuration discriminates between divergent HIV-1 and HIV-2 loop conformations mediated by capsid residue 88. Viral sensitivity to RhTC restriction can be conferred or abolished by mutating position 88. Furthermore, position 88 determines the susceptibility of naturally occurring HIV-1 sequences to restriction. Our results reveal the complex molecular, structural and thermodynamic changes that underlie the ongoing evolutionary race between virus and host.
Active site remodeling switches HIV specificity of antiretroviral TRIMCyp.,Price AJ, Marzetta F, Lammers M, Ylinen LM, Schaller T, Wilson SJ, Towers GJ, James LC Nat Struct Mol Biol. 2009 Oct;16(10):1036-42. Epub 2009 Sep 20. PMID:19767750[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Price AJ, Marzetta F, Lammers M, Ylinen LM, Schaller T, Wilson SJ, Towers GJ, James LC. Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Nat Struct Mol Biol. 2009 Oct;16(10):1036-42. Epub 2009 Sep 20. PMID:19767750 doi:10.1038/nsmb.1667
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