HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity
Summary: HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472100944X |
| _version_ | 1818600091622047744 |
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| author | Qingqing Chai Sunan Li Morgan K. Collins Rongrong Li Iqbal Ahmad Silas F. Johnson Dylan A. Frabutt Zhichang Yang Xiaojing Shen Liangliang Sun Jian Hu Judd F. Hultquist B. Matija Peterlin Yong-Hui Zheng |
| author_facet | Qingqing Chai Sunan Li Morgan K. Collins Rongrong Li Iqbal Ahmad Silas F. Johnson Dylan A. Frabutt Zhichang Yang Xiaojing Shen Liangliang Sun Jian Hu Judd F. Hultquist B. Matija Peterlin Yong-Hui Zheng |
| author_sort | Qingqing Chai |
| collection | DOAJ |
| description | Summary: HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13) as a Nef-associated kinase complex. CycK/CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counteractivity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we generate chimeric proteins between CD8 and SERINC5 to study their response to Nef. Nef not only downregulates but, importantly, also binds to this chimera in an S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery. |
| first_indexed | 2024-12-16T12:29:59Z |
| format | Article |
| id | doaj.art-699aa935e4094bf8a8df9c83d03630a5 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-16T12:29:59Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-699aa935e4094bf8a8df9c83d03630a52022-12-21T22:31:43ZengElsevierCell Reports2211-12472021-08-01366109514HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivityQingqing Chai0Sunan Li1Morgan K. Collins2Rongrong Li3Iqbal Ahmad4Silas F. Johnson5Dylan A. Frabutt6Zhichang Yang7Xiaojing Shen8Liangliang Sun9Jian Hu10Judd F. Hultquist11B. Matija Peterlin12Yong-Hui Zheng13Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USAHarbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Harbin, ChinaDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USAHarbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Harbin, ChinaHarbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Harbin, ChinaDepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA; Department of Biology, Hillsdale College, Hillsdale, MI, USADepartment of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USADepartment of Chemistry, Michigan State University, East Lansing, MI, USADepartment of Chemistry, Michigan State University, East Lansing, MI, USADepartment of Chemistry, Michigan State University, East Lansing, MI, USADepartment of Chemistry, Michigan State University, East Lansing, MI, USA; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USADivision of Infectious Diseases, Northwestern University Feinberg School of Medicine, Chicago, IL, USADepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USAHarbin Veterinary Research Institute, CAAS-Michigan State University Joint Laboratory of Innate Immunity, State Key Laboratory of Veterinary Biotechnology, Chinese Academy of Agricultural Sciences, Harbin, China; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, MI, USA; Corresponding authorSummary: HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13) as a Nef-associated kinase complex. CycK/CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counteractivity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we generate chimeric proteins between CD8 and SERINC5 to study their response to Nef. Nef not only downregulates but, importantly, also binds to this chimera in an S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery.http://www.sciencedirect.com/science/article/pii/S221112472100944XHIV-1Nefrestriction factorsSERINC5CDKcyclin |
| spellingShingle | Qingqing Chai Sunan Li Morgan K. Collins Rongrong Li Iqbal Ahmad Silas F. Johnson Dylan A. Frabutt Zhichang Yang Xiaojing Shen Liangliang Sun Jian Hu Judd F. Hultquist B. Matija Peterlin Yong-Hui Zheng HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity Cell Reports HIV-1 Nef restriction factors SERINC5 CDK cyclin |
| title | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
| title_full | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
| title_fullStr | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
| title_full_unstemmed | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
| title_short | HIV-1 Nef interacts with the cyclin K/CDK13 complex to antagonize SERINC5 for optimal viral infectivity |
| title_sort | hiv 1 nef interacts with the cyclin k cdk13 complex to antagonize serinc5 for optimal viral infectivity |
| topic | HIV-1 Nef restriction factors SERINC5 CDK cyclin |
| url | http://www.sciencedirect.com/science/article/pii/S221112472100944X |
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