Abstract
A new application of antibodies is to use them as macromolecular chaperones. Protein antigens usually have multiple epitopes, thus, there may be a plurality of antibodies binding to one antigen. However, not all antibodies that bind to one antigen could act as a chaperone. Experiments show that some screened anti-human creatine kinase single chain antibodies (scFV) could assist in the folding and stabilizing of the enzyme, while others could not. We built the model of the single chain antibody (scFv-A4) that increased the stability of human creatine kinase (HCK) by the homology modeling method. Epitopes of human creatine kinase were predicted by computer and then the binding of scFv-A4 and HCK was modeled with computer. The calculation results were further combined with the peptide array membrane experiment results to obtain reliable models for the scFv-A4-HCK complex. Based on the above study we gave an explanation about how scFv-A4 could act as a macromolecular chaperone assisting the folding of HCK. This study provides an approach for predicting antigen-antibody binding mode and also a useful theoretical guidance for the study of antibodies' chaperone-like function.
Highlights
In recent years, a number of human diseases, such as Alzheimer’s, Huntington’s, Parkinson’s, and Creutzfeldt-Jakob’s diseases, were reported to be related to the misfolding and aggregation of proteins [1,2]
Molecular chaperones are a kind of protein that are capable of assisting nascent peptides in correctly folding to functional proteins by binding to the folding intermediate to avoid kinetic traps, suppressing aggregation of the substrate [3,4]
Traditional molecular chaperones could be classified according to their molecular weights and sequences to families such as HSP90, HSP70, HSP60 and nucleoplasmin
Summary
A number of human diseases, such as Alzheimer’s, Huntington’s, Parkinson’s, and Creutzfeldt-Jakob’s diseases, were reported to be related to the misfolding and aggregation of proteins [1,2]. Traditional molecular chaperones could be classified according to their molecular weights and sequences to families such as HSP90, HSP70, HSP60 and nucleoplasmin. They have low specificity and react with many kinds of proteins. The use of traditional molecular chaperones as therapeutic molecules for misfolding diseases may have problems such as low efficiency and undesired side-effects. A new field in development is to design or screen specific macromolecules which could be used as chaperones for target proteins, inhibiting their misfolding or coagulation to cure the related protein-misfolding diseases [6,7,8]. Previous researches had shown that some antibodies could excert a chaperone-like function on their antigens [9]
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