Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase
The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SL...
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2021
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oai:doaj.org-article:8c9d393dbd6b4b13a8ba16d21da8b36d2021-12-02T16:08:13ZStructure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase10.1038/s41467-021-24495-w2041-1723https://doaj.org/article/8c9d393dbd6b4b13a8ba16d21da8b36d2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41467-021-24495-whttps://doaj.org/toc/2041-1723The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing.Colin W. GarvieXiaoyun WuMalvina PapanastasiouSooncheol LeeJames FullerGavin R. SchnitzlerSteven W. HornerAndrew BakerTerry ZhangJames P. MullahooLindsay WestlakeStephanie H. HoytMarcus ToetzlMatthew J. RanaghanLuc de WaalJoseph McGaunnBethany KaplanFederica PiccioniXiaoping YangMartin LangeAdrian TersteegenDonald RaymondTimothy A. LewisSteven A. CarrAndrew D. CherniackChristopher T. LemkeMatthew MeyersonHeidi GreulichNature PortfolioarticleScienceQENNature Communications, Vol 12, Iss 1, Pp 1-16 (2021) |
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Science Q Colin W. Garvie Xiaoyun Wu Malvina Papanastasiou Sooncheol Lee James Fuller Gavin R. Schnitzler Steven W. Horner Andrew Baker Terry Zhang James P. Mullahoo Lindsay Westlake Stephanie H. Hoyt Marcus Toetzl Matthew J. Ranaghan Luc de Waal Joseph McGaunn Bethany Kaplan Federica Piccioni Xiaoping Yang Martin Lange Adrian Tersteegen Donald Raymond Timothy A. Lewis Steven A. Carr Andrew D. Cherniack Christopher T. Lemke Matthew Meyerson Heidi Greulich Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase |
| description |
The small molecule DNMDP acts as a velcrin by inducing complex formation between phosphodiesterase PDE3A and SLFN12, which kills cancer cells that express sufficient levels of both proteins. Here, the authors present the cryo-EM structure of the DNMDP-stabilized PDE3A-SLFN12 complex and show that SLFN12 is an RNase. PDE3A binding increases SLFN12 RNase activity, and SLFN12 RNase activity is required for DNMDP-mediated cancer cell killing. |
| format |
article |
| author |
Colin W. Garvie Xiaoyun Wu Malvina Papanastasiou Sooncheol Lee James Fuller Gavin R. Schnitzler Steven W. Horner Andrew Baker Terry Zhang James P. Mullahoo Lindsay Westlake Stephanie H. Hoyt Marcus Toetzl Matthew J. Ranaghan Luc de Waal Joseph McGaunn Bethany Kaplan Federica Piccioni Xiaoping Yang Martin Lange Adrian Tersteegen Donald Raymond Timothy A. Lewis Steven A. Carr Andrew D. Cherniack Christopher T. Lemke Matthew Meyerson Heidi Greulich |
| author_facet |
Colin W. Garvie Xiaoyun Wu Malvina Papanastasiou Sooncheol Lee James Fuller Gavin R. Schnitzler Steven W. Horner Andrew Baker Terry Zhang James P. Mullahoo Lindsay Westlake Stephanie H. Hoyt Marcus Toetzl Matthew J. Ranaghan Luc de Waal Joseph McGaunn Bethany Kaplan Federica Piccioni Xiaoping Yang Martin Lange Adrian Tersteegen Donald Raymond Timothy A. Lewis Steven A. Carr Andrew D. Cherniack Christopher T. Lemke Matthew Meyerson Heidi Greulich |
| author_sort |
Colin W. Garvie |
| title |
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase |
| title_short |
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase |
| title_full |
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase |
| title_fullStr |
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase |
| title_full_unstemmed |
Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase |
| title_sort |
structure of pde3a-slfn12 complex reveals requirements for activation of slfn12 rnase |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/8c9d393dbd6b4b13a8ba16d21da8b36d |
| work_keys_str_mv |
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