Tetrahymena thermophila Granule Lattice Protein 3 Improves Solubility of Sexual Stage Malaria Antigens Expressed in Escherichia coli

Author:

Akkale CengizORCID,Cassidy-Hanley Donna Marie,Clark Theodore G.ORCID

Abstract

AbstractThe requirement for low cost manufacturing makes bacterial cells a logical platform for the production of recombinant subunit vaccines for malaria. However, protein solubility has been a major stumbling block with prokaryotic expression systems. Notable examples include the transmission blocking vaccine candidates, Pfs25 and Pfs48/45, which are almost entirely insoluble when expressed as recombinant proteins in Escherichia coli. Various solubility tags have been used with limited success in improving solubility, although recent studies with granule lattice protein 1 (Grl1p) from the ciliated protozoan, Tetrahymena thermophila, have shown promise. Here, we examine a related solubility tag, granule lattice protein 3 (Grl3p) from T. thermophila, and compare it to both Grl1p and the well-studied maltose binding protein (MBP) used to improve the solubility of multiple protein targets. We find that Grl3p performs comparably to Grl1p when linked to Pfs25 but significantly improves solubility when paired with Pfs48/45.

Publisher

Cold Spring Harbor Laboratory

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