Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.
TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-08-01
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| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001062&type=printable |
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| author | Laura M J Ylinen Amanda J Price Jane Rasaiyaah Stéphane Hué Nicola J Rose Flavia Marzetta Leo C James Greg J Towers |
| author_facet | Laura M J Ylinen Amanda J Price Jane Rasaiyaah Stéphane Hué Nicola J Rose Flavia Marzetta Leo C James Greg J Towers |
| author_sort | Laura M J Ylinen |
| collection | DOAJ |
| description | TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations. |
| format | Article |
| id | doaj-art-0a2cec071f2d4a209356b0a4fedcc632 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2010-08-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-0a2cec071f2d4a209356b0a4fedcc6322025-08-20T03:07:20ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742010-08-0168e100106210.1371/journal.ppat.1001062Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.Laura M J YlinenAmanda J PriceJane RasaiyaahStéphane HuéNicola J RoseFlavia MarzettaLeo C JamesGreg J TowersTRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001062&type=printable |
| spellingShingle | Laura M J Ylinen Amanda J Price Jane Rasaiyaah Stéphane Hué Nicola J Rose Flavia Marzetta Leo C James Greg J Towers Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. PLoS Pathogens |
| title | Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. |
| title_full | Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. |
| title_fullStr | Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. |
| title_full_unstemmed | Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. |
| title_short | Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. |
| title_sort | conformational adaptation of asian macaque trimcyp directs lineage specific antiviral activity |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1001062&type=printable |
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