Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases
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ABSTRACT:
SUBMITTER: John Kuriyan
PROVIDER: EMPIAR-10544 | biostudies-other |
REPOSITORIES: biostudies-other
Publications
Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases.
Kondo Yasushi Y Ognjenović Jana J Banerjee Saikat S Karandur Deepti D Merk Alan A Kulhanek Kayla K Wong Kathryn K Roose Jeroen P JP Subramaniam Sriram S Kuriyan John J
Science (New York, N.Y.) 20190919 6461
Raf kinases are important cancer drug targets. Paradoxically, many B-Raf inhibitors induce the activation of Raf kinases. Cryo-electron microscopy structural analysis of a phosphorylated B-Raf kinase domain dimer in complex with dimeric 14-3-3, at a resolution of ~3.9 angstroms, shows an asymmetric arrangement in which one kinase is in a canonical "active" conformation. The distal segment of the C-terminal tail of this kinase interacts with, and blocks, the active site of the cognate kinase in t ...[more]
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