Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication.
The RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IP...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2015-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4565553?pdf=render |
| _version_ | 1828352695796236288 |
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| author | Bryan Korithoski Oralia Kolaczkowski Krishanu Mukherjee Reema Kola Chandra Earl Bryan Kolaczkowski |
| author_facet | Bryan Korithoski Oralia Kolaczkowski Krishanu Mukherjee Reema Kola Chandra Earl Bryan Kolaczkowski |
| author_sort | Bryan Korithoski |
| collection | DOAJ |
| description | The RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IPS1 through binding between the twin caspase activation and recruitment domains (CARDs) on the RLR and a homologous CARD on IPS1, it is less clear which specific RLR CARD(s) are required for this interaction, and almost nothing is known about how the RLR-IPS1 interaction evolved. In contrast to what has been observed in the presence of immune-modulating K63-linked polyubiquitin, here we show that-in the absence of ubiquitin-it is the first CARD domain of human RIG-I and MDA5 (CARD1) that binds directly to IPS1 CARD, and not the second (CARD2). Although the RLRs originated in the earliest animals, both the IPS1 gene and the twin-CARD domain architecture of RIG-I and MDA5 arose much later in the deuterostome lineage, probably through a series of tandem partial-gene duplication events facilitated by tight clustering of RLRs and IPS1 in the ancestral deuterostome genome. Functional differentiation of RIG-I CARD1 and CARD2 appears to have occurred early during this proliferation of RLR and related CARDs, potentially driven by adaptive coevolution between RIG-I CARD domains and IPS1 CARD. However, functional differentiation of MDA5 CARD1 and CARD2 occurred later. These results fit a general model in which duplications of protein-protein interaction domains into novel gene contexts could facilitate the expansion of signaling networks and suggest a potentially important role for functionally-linked gene clusters in generating novel immune-signaling pathways. |
| first_indexed | 2024-04-14T01:56:53Z |
| format | Article |
| id | doaj.art-27841bd9ac7045b39b3c34317c726fb0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-14T01:56:53Z |
| publishDate | 2015-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-27841bd9ac7045b39b3c34317c726fb02022-12-22T02:18:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01109e013727610.1371/journal.pone.0137276Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication.Bryan KorithoskiOralia KolaczkowskiKrishanu MukherjeeReema KolaChandra EarlBryan KolaczkowskiThe RIG-like receptors (RLRs) are related proteins that identify viral RNA in the cytoplasm and activate cellular immune responses, primarily through direct protein-protein interactions with the signal transducer, IPS1. Although it has been well established that the RLRs, RIG-I and MDA5, activate IPS1 through binding between the twin caspase activation and recruitment domains (CARDs) on the RLR and a homologous CARD on IPS1, it is less clear which specific RLR CARD(s) are required for this interaction, and almost nothing is known about how the RLR-IPS1 interaction evolved. In contrast to what has been observed in the presence of immune-modulating K63-linked polyubiquitin, here we show that-in the absence of ubiquitin-it is the first CARD domain of human RIG-I and MDA5 (CARD1) that binds directly to IPS1 CARD, and not the second (CARD2). Although the RLRs originated in the earliest animals, both the IPS1 gene and the twin-CARD domain architecture of RIG-I and MDA5 arose much later in the deuterostome lineage, probably through a series of tandem partial-gene duplication events facilitated by tight clustering of RLRs and IPS1 in the ancestral deuterostome genome. Functional differentiation of RIG-I CARD1 and CARD2 appears to have occurred early during this proliferation of RLR and related CARDs, potentially driven by adaptive coevolution between RIG-I CARD domains and IPS1 CARD. However, functional differentiation of MDA5 CARD1 and CARD2 occurred later. These results fit a general model in which duplications of protein-protein interaction domains into novel gene contexts could facilitate the expansion of signaling networks and suggest a potentially important role for functionally-linked gene clusters in generating novel immune-signaling pathways.http://europepmc.org/articles/PMC4565553?pdf=render |
| spellingShingle | Bryan Korithoski Oralia Kolaczkowski Krishanu Mukherjee Reema Kola Chandra Earl Bryan Kolaczkowski Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. PLoS ONE |
| title | Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. |
| title_full | Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. |
| title_fullStr | Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. |
| title_full_unstemmed | Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. |
| title_short | Evolution of a Novel Antiviral Immune-Signaling Interaction by Partial-Gene Duplication. |
| title_sort | evolution of a novel antiviral immune signaling interaction by partial gene duplication |
| url | http://europepmc.org/articles/PMC4565553?pdf=render |
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