Compositions & methods for monitoring and altering protein folding and solubility

A method for screening for mutations in a target protein sequence that alter solubility and/or folding of said target protein, comprising:

• a) introducing one or more mutations into the nucleic acid sequence that encodes said target protein;
• b) expressing the mutant target protein as a fusion protein, wherein said fusion protein comprises a Tat leader signal, the target protein, and a selectable marker, wherein correct folding of said target protein confers selectable activity upon expression of said fusion protein in said host cell;
• and
• d) selecting those host cells in which the selectable activity is expressed, whereby expression of said selectable activity indicates solubility and/or proper folding of the target protein,

A method for screening for mutations in a target protein sequence that alters solubility and/or folding of said target protein, comprising:

• a) providing a library of nucleic acid sequences encoding fusion proteins, wherein said fusion proteins each comprise a Tat leader signal, an altered target protein, and a selectable marker protein;
• b) expressing said fusion proteins in host cells, wherein correct folding of said fusion proteins confers selectable activity upon expression of said fusion protein in said host cells;
• and
• c) screening for those host cells that express said selectable activity, whereby expression of said selectable activity indicates solubility and/or proper folding of the target protein.