Structure of PDE3A-SLFN12 complex reveals requirements for activation of SLFN12 RNase

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...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
Materias:
Science
Q
Acceso en línea:https://doaj.org/article/8c9d393dbd6b4b13a8ba16d21da8b36d
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario: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.

Ejemplares similares