University of Sussex

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Braf mutants.eds (8.25 MB)

Thermal Shift Assay for BRAF mutants for paper: Recognition of BRAF by CDC37 and Re-evaluation of the Activation mechanism for the Class 2 BRAF-L597R Mutant

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posted on 2022-06-29, 12:30 authored by Chrisostomos ProdromouChrisostomos Prodromou, Jasmeen OberoiJasmeen Oberoi, Rhodri M. L. Morgan, Dennis Bjorklund, Panagiota A Galliou, Katie L.I.M. Day

Data for paper published in Biomolecules June 2022 

Raw data for Thermal shift asay of BRAF mutants. Use the LightCycler 480 SW 1.5 software or similar to access the data files.


The kinome specific co-chaperone, CDC37, is responsible for delivering BRAF to the Hsp90 complex, where it is then translocated to the RAS complex at the plasma membrane for RAS mediated dimerization and subsequent activation. We identify a bipartite interaction between CDC37 and BRAF and delimitate the essential structural elements of CDC37 involved in BRAF recognition. We find an extended and conserved CDC37 motif, 20HPNID---SL--W31, responsible for recognising the C-lobe of BRAF kinase domain, while the C-terminal domain of CDC37 is responsible for the second of the bipartite interaction with BRAF.  We show that dimerization of BRAF, independent of nucleotide binding, can act as a potent signal that prevents CDC37 recognition and discuss the implications of mutations in BRAF and the consequences on signalling in a clinical setting, particularly for class 2 BRAF mutations. 


Recognition, activation and targeted degradation of protein kinases clients by the HSP90-molecular chaperone

Wellcome Trust

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