Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex.
Rotaviruses (RVs) are the leading cause of severe gastroenteritis in young children, accounting for half a million deaths annually worldwide. RV encodes non-structural protein 1 (NSP1), a well-characterized interferon (IFN) antagonist, which facilitates virus replication by mediating the degradation...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-10-01
|
| Series: | PLoS Pathogens |
| Online Access: | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005929&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849765388549619712 |
|---|---|
| author | Siyuan Ding Nancie Mooney Bin Li Marcus R Kelly Ningguo Feng Alexander V Loktev Adrish Sen John T Patton Peter K Jackson Harry B Greenberg |
| author_facet | Siyuan Ding Nancie Mooney Bin Li Marcus R Kelly Ningguo Feng Alexander V Loktev Adrish Sen John T Patton Peter K Jackson Harry B Greenberg |
| author_sort | Siyuan Ding |
| collection | DOAJ |
| description | Rotaviruses (RVs) are the leading cause of severe gastroenteritis in young children, accounting for half a million deaths annually worldwide. RV encodes non-structural protein 1 (NSP1), a well-characterized interferon (IFN) antagonist, which facilitates virus replication by mediating the degradation of host antiviral factors including IRF3 and β-TrCP. Here, we utilized six human and animal RV NSP1s as baits and performed tandem-affinity purification coupled with high-resolution mass spectrometry to comprehensively characterize NSP1-host protein interaction network. Multiple Cullin-RING ubiquitin ligase (CRL) complexes were identified. Importantly, inhibition of cullin-3 (Cul3) or RING-box protein 1 (Rbx1), by siRNA silencing or chemical perturbation, significantly impairs strain-specific NSP1-mediated β-TrCP degradation. Mechanistically, we demonstrate that NSP1 localizes to the Golgi with the host Cul3-Rbx1 CRL complex, which targets β-TrCP and NSP1 for co-destruction at the proteasome. Our study uncovers a novel mechanism that RV employs to promote β-TrCP turnover and provides molecular insights into virus-mediated innate immunity inhibition. |
| format | Article |
| id | doaj-art-1a4783667f544669ba3c3d44d78db076 |
| institution | DOAJ |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2016-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-1a4783667f544669ba3c3d44d78db0762025-08-20T03:04:53ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-10-011210e100592910.1371/journal.ppat.1005929Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex.Siyuan DingNancie MooneyBin LiMarcus R KellyNingguo FengAlexander V LoktevAdrish SenJohn T PattonPeter K JacksonHarry B GreenbergRotaviruses (RVs) are the leading cause of severe gastroenteritis in young children, accounting for half a million deaths annually worldwide. RV encodes non-structural protein 1 (NSP1), a well-characterized interferon (IFN) antagonist, which facilitates virus replication by mediating the degradation of host antiviral factors including IRF3 and β-TrCP. Here, we utilized six human and animal RV NSP1s as baits and performed tandem-affinity purification coupled with high-resolution mass spectrometry to comprehensively characterize NSP1-host protein interaction network. Multiple Cullin-RING ubiquitin ligase (CRL) complexes were identified. Importantly, inhibition of cullin-3 (Cul3) or RING-box protein 1 (Rbx1), by siRNA silencing or chemical perturbation, significantly impairs strain-specific NSP1-mediated β-TrCP degradation. Mechanistically, we demonstrate that NSP1 localizes to the Golgi with the host Cul3-Rbx1 CRL complex, which targets β-TrCP and NSP1 for co-destruction at the proteasome. Our study uncovers a novel mechanism that RV employs to promote β-TrCP turnover and provides molecular insights into virus-mediated innate immunity inhibition.https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005929&type=printable |
| spellingShingle | Siyuan Ding Nancie Mooney Bin Li Marcus R Kelly Ningguo Feng Alexander V Loktev Adrish Sen John T Patton Peter K Jackson Harry B Greenberg Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. PLoS Pathogens |
| title | Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. |
| title_full | Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. |
| title_fullStr | Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. |
| title_full_unstemmed | Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. |
| title_short | Comparative Proteomics Reveals Strain-Specific β-TrCP Degradation via Rotavirus NSP1 Hijacking a Host Cullin-3-Rbx1 Complex. |
| title_sort | comparative proteomics reveals strain specific β trcp degradation via rotavirus nsp1 hijacking a host cullin 3 rbx1 complex |
| url | https://journals.plos.org/plospathogens/article/file?id=10.1371/journal.ppat.1005929&type=printable |
| work_keys_str_mv | AT siyuanding comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT nanciemooney comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT binli comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT marcusrkelly comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT ningguofeng comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT alexandervloktev comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT adrishsen comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT johntpatton comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT peterkjackson comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex AT harrybgreenberg comparativeproteomicsrevealsstrainspecificbtrcpdegradationviarotavirusnsp1hijackingahostcullin3rbx1complex |