Hsp70 is a two-domain molecular chaperone involved in maintaining cellular homeostasis. Its function results from mechanical changes caused by hydrolysis of ATP in the N-terminal nucleotide binding domain (NBD) that alter the client binding affinity of the C-terminal substrate binding domain (SBD). To study the dynamics of client binding, we linked the C-terminus of Hsp70 to a client peptide by means of an unstructured, chimeric linker. Utilizing coarse-grained simulations in concert with laser optical tweezer experiments, we investigated the effects of force applied at various points of the linker on the unfolding of the SBD. Initial results indicate that stabilization varies across the SBD β-sandwich subdomain: the N-terminal β strands can detach before or after disruption of the rest of the subdomain.

Allosteric mechanism of peptide release in the molecular chaperone Hsp70

255th National Meeting (2018)

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