Summary for 7Z37
| Entry DOI | 10.2210/pdb7z37/pdb |
| EMDB information | 14472 |
| Descriptor | Heat shock protein HSP 90-beta, RAF proto-oncogene serine/threonine-protein kinase, Hsp90 co-chaperone Cdc37, ... (4 entities in total) |
| Functional Keywords | raf1-hsp90-cdc37, complex, proto-oncogene, transferase, serine/threonine kinase, cancer, chaperone |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 290702.39 |
| Authors | Mesa, P.,Garcia-Alonso, S.,Barbacid, M.,Montoya, G. (deposition date: 2022-03-01, release date: 2022-09-14, Last modification date: 2022-09-28) |
| Primary citation | Garcia-Alonso, S.,Mesa, P.,Ovejero, L.P.,Aizpurua, G.,Lechuga, C.G.,Zarzuela, E.,Santiveri, C.M.,Sanclemente, M.,Munoz, J.,Musteanu, M.,Campos-Olivas, R.,Martinez-Torrecuadrada, J.,Barbacid, M.,Montoya, G. Structure of the RAF1-HSP90-CDC37 complex reveals the basis of RAF1 regulation. Mol.Cell, 82:3438-3452.e8, 2022 Cited by PubMed Abstract: 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. PubMed: 36055235DOI: 10.1016/j.molcel.2022.08.012 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.67 Å) |
Structure validation
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