Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase
oleh: 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
| Format: | Article |
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| Diterbitkan: | Nature Portfolio 2021-07-01 |
Deskripsi
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.