The Effect of Stability and Surface Charge Distribution on Secretion of Bovine Pancreatic Trypsin Inhibitor From Yeast
Kowalski, Jean Marie
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https://hdl.handle.net/2142/82452
Description
Title
The Effect of Stability and Surface Charge Distribution on Secretion of Bovine Pancreatic Trypsin Inhibitor From Yeast
Author(s)
Kowalski, Jean Marie
Issue Date
1998
Doctoral Committee Chair(s)
Karl Dane Wittrup
Department of Study
Chemical Engineering
Discipline
Chemical Engineering
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Microbiology
Language
eng
Abstract
Biophysical characterization of the BPTI mutants shows that removal of charges results in a drop in the effective number of ionic binding sites, as analyzed by binding of the molecule to a cation exchange column. Removal of the charge on the uncharged face of the molecule results in a dramatic increase in the relative hydrophobicity of the molecule, compared to removal of other charges. On the basis of these data, we suggest that the ER acts as a cation exchange column and that the ER quality control apparatus decreases the yield of proteins with longer ER residence times. Generally, removing charges decreases residence times and therefore the amount of protein degraded by the quality control apparatus, resulting in significant yield increases. However, if charge removal results in increased protein hydrophobicity, it could result in increased recognition and degradation by the quality control apparatus.
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