Electrostatics Drive the Molecular Chaperone BiP to Preferentially Bind Oligomerized States of a Client Protein.

ABSTRACT: Hsp70 chaperones bind short monomeric peptides with a weak characteristic affinity in the low micromolar range, but can also bind some aggregates, fibrils, and amyloids, with low nanomolar affinity. While this differential affinity enables Hsp70 to preferentially target potentially toxic aggregates, it is unknown how a chaperone can differentiate between monomeric and aggregated states of a client protein and why preferential binding is only observed for some aggregated clients but not others. Here we examine the interaction of BiP (the Hsp70 paralog in the endoplasmic reticulum) with the client proIGF2, the pro-protein form of IGF2 that includes a long and mostly disordered E-peptide region that promotes proIGF2 oligomerization. By dissecting the mechanism by which BiP targets proIGF2 and

SUBMITTER: Deans EE 

PROVIDER: S-EPMC10189785 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature