7z38

Structure of the RAF1-HSP90-CDC37 complex (RHC-I)

spinqualitylabelsall models 7z38, resolution 3.16Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7z38 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.16Å Ligands: ATP, MG, SEP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HS90B_HUMAN Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function. Publication Abstract from PubMed RAF kinases are RAS-activated enzymes that initiate signaling through the MAPK cascade to control cellular proliferation, differentiation, and survival. Here, we describe the structure of the full-length RAF1 protein in complex with HSP90 and CDC37 obtained by cryoelectron microscopy. The reconstruction reveals a RAF1 kinase with an unfolded N-lobe separated from its C-lobe. The hydrophobic core of the N-lobe is trapped in the HSP90 dimer, while CDC37 wraps around the chaperone and interacts with the N- and C-lobes of the kinase. The structure indicates how CDC37 can discriminate between the different members of the RAF family. Our structural analysis also reveals that the folded RAF1 assembles with 14-3-3 dimers, suggesting that after folding RAF1 follows a similar activation as B-RAF. Finally, disruption of the interaction between CDC37 and the DFG segment of RAF1 unveils potential vulnerabilities in attempting the pharmacological degradation of RAF1 for therapeutic purposes. Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation.,Garcia-Alonso S, Mesa P, Ovejero LP, Aizpurua G, Lechuga CG, Zarzuela E, Santiveri CM, Sanclemente M, Munoz J, Musteanu M, Campos-Olivas R, Martinez-Torrecuadrada J, Barbacid M, Montoya G Mol Cell. 2022 Sep 15;82(18):3438-3452.e8. doi: 10.1016/j.molcel.2022.08.012. , Epub 2022 Sep 1. PMID:36055235 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Heat Shock Protein structures

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