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| | ==SmBz bound to Cyclophilin A== | | ==SmBz bound to Cyclophilin A== |
| - | <StructureSection load='4ipz' size='340' side='right' caption='[[4ipz]], [[Resolution|resolution]] 1.67Å' scene=''> | + | <StructureSection load='4ipz' size='340' side='right'caption='[[4ipz]], [[Resolution|resolution]] 1.67Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ipz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4IPZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ipz]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Tolypocladium_inflatum Tolypocladium inflatum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IPZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IPZ 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=1JM:4-CARBOXY-N-METHYL-D-PHENYLALANINE'>1JM</scene>, <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=1JM:4-CARBOXY-N-METHYL-D-PHENYLALANINE'>1JM</scene>, <scene name='pdbligand=ABA:ALPHA-AMINOBUTYRIC+ACID'>ABA</scene>, <scene name='pdbligand=BMT:4-METHYL-4-[(E)-2-BUTENYL]-4,N-METHYL-THREONINE'>BMT</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=MLE:N-METHYLLEUCINE'>MLE</scene>, <scene name='pdbligand=MVA:N-METHYLVALINE'>MVA</scene>, <scene name='pdbligand=SAR:SARCOSINE'>SAR</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=4ipz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ipz OCA], [https://pdbe.org/4ipz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ipz RCSB], [https://www.ebi.ac.uk/pdbsum/4ipz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ipz ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPIA, CYPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4ipz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ipz OCA], [http://pdbe.org/4ipz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ipz RCSB], [http://www.ebi.ac.uk/pdbsum/4ipz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ipz ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN]] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. | + | [https://www.uniprot.org/uniprot/PPIA_HUMAN PPIA_HUMAN] PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Peptidylprolyl isomerase]] | + | [[Category: Large Structures]] |
| - | [[Category: Jacques, D A]] | + | [[Category: Tolypocladium inflatum]] |
| - | [[Category: James, L C]] | + | [[Category: Jacques DA]] |
| - | [[Category: Price, A J]] | + | [[Category: James LC]] |
| - | [[Category: Cyclophilin fold]] | + | [[Category: Price AJ]] |
| - | [[Category: Cyclosporine some]]
| + | |
| - | [[Category: Isomerase-isomerase inhibitor complex]]
| + | |
| - | [[Category: Peptidyl-prolyl isomerase]]
| + | |
| Structural highlights
4ipz is a 2 chain structure with sequence from Homo sapiens and Tolypocladium inflatum. 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 |
Function
PPIA_HUMAN PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Publication Abstract from PubMed
Human immunodeficiency virus (HIV)-1 is able to replicate in primary human macrophages without stimulating innate immunity despite reverse transcription of genomic RNA into double-stranded DNA, an activity that might be expected to trigger innate pattern recognition receptors. We reasoned that if correctly orchestrated HIV-1 uncoating and nuclear entry is important for evasion of innate sensors then manipulation of specific interactions between HIV-1 capsid and host factors that putatively regulate these processes should trigger pattern recognition receptors and stimulate type 1 interferon (IFN) secretion. Here we show that HIV-1 capsid mutants N74D and P90A, which are impaired for interaction with cofactors cleavage and polyadenylation specificity factor subunit 6 (CPSF6) and cyclophilins (Nup358 and CypA), respectively, cannot replicate in primary human monocyte-derived macrophages because they trigger innate sensors leading to nuclear translocation of NF-kappaB and IRF3, the production of soluble type 1 IFN and induction of an antiviral state. Depletion of CPSF6 with short hairpin RNA expression allows wild-type virus to trigger innate sensors and IFN production. In each case, suppressed replication is rescued by IFN-receptor blockade, demonstrating a role for IFN in restriction. IFN production is dependent on viral reverse transcription but not integration, indicating that a viral reverse transcription product comprises the HIV-1 pathogen-associated molecular pattern. Finally, we show that we can pharmacologically induce wild-type HIV-1 infection to stimulate IFN secretion and an antiviral state using a non-immunosuppressive cyclosporine analogue. We conclude that HIV-1 has evolved to use CPSF6 and cyclophilins to cloak its replication, allowing evasion of innate immune sensors and induction of a cell-autonomous innate immune response in primary human macrophages.
HIV-1 evades innate immune recognition through specific cofactor recruitment.,Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C, Hilditch L, Jacques DA, Selwood DL, James LC, Noursadeghi M, Towers GJ Nature. 2013 Nov 21;503(7476):402-5. doi: 10.1038/nature12769. Epub 2013 Nov 6. PMID:24196705[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C, Hilditch L, Jacques DA, Selwood DL, James LC, Noursadeghi M, Towers GJ. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature. 2013 Nov 21;503(7476):402-5. doi: 10.1038/nature12769. Epub 2013 Nov 6. PMID:24196705 doi:http://dx.doi.org/10.1038/nature12769
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