Today, I saw an interesting question to share with you here.
What if the protein can't be expressed and purified in E. coli system?
Here are a few things can be done to solve the problem:
(1) codon optimization is recommended if it has not been;
(2) remove the transmembrane region and signal peptide region;
(3) try to express truncated domains of the protein;
(4) try different tags to increase the expression level;
(5) try different expression systems (e.g. insect cell system for certain proteins).
You can find more information about protein expression here.