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ITC data for CDC37-BRAF interactions for paper: Recognition of BRAF by CDC37 and Re-evaluation of the Activation mechanism for the Class 2 BRAF-L597R Mutant

posted on 29.06.2022, 12:29 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 

Isothermal Titration Calorimetry results for CDC37-BRAF interactions. dil in the filename donates the heat of dilution. Heats of dilution are in to buffer. Pairs with the same date donate a set of experiments. After the date the interacting partner proteins or small molecule is shown. Use Origin program 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. 


Wellcome Trust senior investigator award 095605/Z/11/Z (L.H.P).