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Title 

Designing an antibody-based chaperoning system through programming the binding and release of the folding intermediate

Authors 

T LiuC SunC LiJinhyuk LeeY D ParkY ZhangS Li

Publisher 

American Chemical Society

Issue Date 

2016

Citation 

ACS Chemical Biology, vol. 11, no. 4, pp. 1090-1097

Abstract 

The protein folding pathway consists of sequential intramolecular interactions, while chaperones exert their functions either by stabilizing folding intermediates or by preventing nonspecific intermolecular interactions, which are often associated with aggregation involving exposed hydrophobic residues in folding intermediates. As chaperones do not possess specificity for individual client proteins, we designed an antibody-based chaperoning system to mimic the sequential binding and release of client proteins undergoing folding. The single-chain variable fragment of antibody (scFv) A4 binds to human muscle creatine kinase (HCK) and prevents it from aggregating. The slow dissociation of HCK from A4 resulted in delayed but eventually high-quality refolding, as reflected by the higher recovery of enzymatic activity as well as abolished aggregation. Peptide P6, a sequence in HCK involved in A4 binding, competes with HCK, promotes its dissociation from A4, and accelerates the rate of high-quality refolding. The sequential addition of A4 and P6 is essential for the chaperoning effect. The programmed binding/release method can also be applied to refold HCK from inclusion bodies. Because the association/dissociation of the folding intermediate with the antibody is highly specific, the method can be used to design tailored refolding systems and to investigate chaperoning effects on protein folding/aggregation in a sequence-specific manner.

ISSN 

1554-8929

Link 

http://dx.doi.org/10.1021/acschembio.6b00191

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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