Please use this identifier to cite or link to this item:
|Title:||Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer|
|Authors:||Berger, Stephanie;Procko, Erik;Margineantu, Daciana;Lee, Erinna F;Shen, Betty W;Zelter, Alex;Silva, Daniel-Adriano;Chawla, Kusum;Herold, Marco J;Garnier, Jean-Marc;Johnson, Richard;MacCoss, Michael J;Lessene, Guillaume;Davis, Trisha N;Stayton, Patrick S;Stoddard, Barry L;Fairlie, W Douglas;Hockenbery, David M;Baker, David|
|Citation:||eLIFE 2016; 5: e20352|
|Abstract:||Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes.|
computational protein design
|Appears in Collections:||Journal articles|
Files in This Item:
There are no files associated with this item.
Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.