The Effect of Alpha-mating Factor Secretion Signal Mutations on Recombinant Protein Expression in Pichia pastoris

Poster Number

37

Lead Author Major

Pre-Dentistry

Format

Poster Presentation

Faculty Mentor Name

Joan Lin-Cereghino

Faculty Mentor Department

Biological Sciences

Additional Faculty Mentor Name

Geoffrey Lin-Cereghino

Abstract/Artist Statement

Pichia pastoris is a species of methylotrophic yeast used as an expression system to produce and secrete foreign proteins. Secretion of such heterologous proteins requires fusion of alphamating factor secretion signal (Mat-alpha) to the N-terminus of the protein construct. The secretion signal acts as an "address label" that helps direct the protein to be secreted out of the cell. Here, we describe how the removal and addition of specific amino acids in the 85 amino acid Mat-alpha secretion signal affects the secretion of horseradish peroxidase (HRP), which was used as a reporter. Computer modeling of the Mat-alpha secondary structure created in the Lin-Cereghino lab as well as bioinformatics resources were used to create mutant Mat-alpha sequences in order to comprehend how the signal functions. The results allowed us to not only understand the potential contribution of each segment, but also ponder possibilities to achieve higher levels of secretion. Several mutant signals were found to provide significantly greater secretion levels of HRP than the wild type Mat-alpha, indicating that the targeted amino acids could play an essential role in the export pathway.

Location

DeRosa University Center, Ballroom

Start Date

26-4-2014 2:00 PM

End Date

26-4-2014 4:00 PM

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Apr 26th, 2:00 PM Apr 26th, 4:00 PM

The Effect of Alpha-mating Factor Secretion Signal Mutations on Recombinant Protein Expression in Pichia pastoris

DeRosa University Center, Ballroom

Pichia pastoris is a species of methylotrophic yeast used as an expression system to produce and secrete foreign proteins. Secretion of such heterologous proteins requires fusion of alphamating factor secretion signal (Mat-alpha) to the N-terminus of the protein construct. The secretion signal acts as an "address label" that helps direct the protein to be secreted out of the cell. Here, we describe how the removal and addition of specific amino acids in the 85 amino acid Mat-alpha secretion signal affects the secretion of horseradish peroxidase (HRP), which was used as a reporter. Computer modeling of the Mat-alpha secondary structure created in the Lin-Cereghino lab as well as bioinformatics resources were used to create mutant Mat-alpha sequences in order to comprehend how the signal functions. The results allowed us to not only understand the potential contribution of each segment, but also ponder possibilities to achieve higher levels of secretion. Several mutant signals were found to provide significantly greater secretion levels of HRP than the wild type Mat-alpha, indicating that the targeted amino acids could play an essential role in the export pathway.