8CHF

cryo-EM Structure of Craf:14-3-3:Mek1

Summary for 8CHF

• Entry DOI: 10.2210/pdb8chf/pdb
• EMDB information: 16660
• Descriptor: RAF proto-oncogene serine/threonine-protein kinase, 14-3-3 protein zeta isoform X1, Dual specificity mitogen-activated protein kinase kinase 1, ... (4 entities in total)
• Functional Keywords: kinase, structural protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 290178.60

Authors

Dedden, D.,Ulrich, G. (deposition date: 2023-02-07, release date: 2024-02-21, Last modification date: 2024-11-13)

Primary citation

Dedden, D.,Nitsche, J.,Schneider, E.V.,Thomsen, M.,Schwarz, D.,Leuthner, B.,Gradler, U.
Cryo-EM Structures of CRAF 2 /14-3-3 2 and CRAF 2 /14-3-3 2 /MEK1 2 Complexes.
J.Mol.Biol., 436:168483-168483, 2024

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) 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.

PubMed: 38331211
DOI: 10.1016/j.jmb.2024.168483

Experimental method

ELECTRON MICROSCOPY (4.25 Å)