ITC raw data files for CDC37-BRAF interactions and Thermal shift assays for BRAF mutants for paper: Recognition of BRAF by CDC37 and Re-evaluation of the Activation mechanism for the Class 2 BRAF-L597R Mutant
Data for paper published in Biomolecules June 2022
Isothermal titration experoments between CDC37 and BRAF. Data donated with dil in the filename are the heats of dilution (control). Each experiment consists of a pair of data sets are pairs are identified by date.
Thermal shift assays are for BRAF mutants
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.