The Effect of Stability and Surface Charge Distribution on Secretion of Bovine Pancreatic Trypsin Inhibitor From Yeast

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemical Engineering

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Kowalski, Jean Marie

Contributors dc:contributor

• Karl Dane Wittrup

• Biology, Microbiology

Language dc:language

eng

Identifier

(MiAaPQ)AAI9904514

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/82452