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Title | Cryo-EM Structures of CRAF/14-3-3 and CRAF/14-3-3/MEK1 Complexes. |
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Journal, issue, pages | J Mol Biol, Vol. 436, Issue 6, Page 168483, Year 2024 |
Publish date | Feb 7, 2024 |
Authors | Dirk Dedden / Julius Nitsche / Elisabeth V Schneider / Maren Thomsen / Daniel Schwarz / Birgitta Leuthner / Ulrich Grädler / |
PubMed Abstract | RAF protein kinases are essential effectors in the MAPK pathway and are important cancer drug targets. Structural understanding of RAF activation is so far based on cryo-electron microscopy (cryo-EM) ...RAF protein kinases are essential effectors in the MAPK pathway and are important cancer drug targets. Structural understanding of RAF activation is so far based on cryo-electron microscopy (cryo-EM) and X-ray structures of BRAF in different conformational states as inactive or active complexes with KRAS, 14-3-3 and MEK1. In this study, we have solved the first cryo-EM structures of CRAF/14-3-3 at 3.4 Å resolution and CRAF/14-3-3/MEK1 at 4.2 Å resolution using CRAF kinase domain expressed as constitutively active Y340D/Y341D mutant in insect cells. The overall architecture of our CRAF/14-3-3 and CRAF/14-3-3/MEK1 cryo-EM structures is highly similar to corresponding BRAF structures in complex with 14-3-3 or 14-3-3/MEK1 and represent the activated dimeric RAF conformation. Our CRAF cryo-EM structures provide additional insights into structural understanding of the activated CRAF/14-3-3/MEK1 complex. |
External links | J Mol Biol / PubMed:38331211 |
Methods | EM (single particle) |
Resolution | 3.46 - 4.25 Å |
Structure data | EMDB-16660, PDB-8chf: EMDB-16779, PDB-8cpd: |
Chemicals | ChemComp-29L: |
Source |
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Keywords | STRUCTURAL PROTEIN / Kinase / CYTOKINE / Complex |