| Membrane bound receptors are complex and difficult to work with from a molecular biology perspective, because typically they are large, glycosylated, insoluble, and often multimeric. Therefore, few have been studied crystallographically, but they are potential therapeutic targets because they serve as entry points to many biological processes that have been implicated in diseases such as cancer. The crystal structures would be helpful in the development of a therapeutic inhibitor against these receptors. One solution to this problem would be to break up the receptor into soluble functional units that are easier to work with. I have been studying the membrane bound receptor HER3 as potential therapeutic target against breast cancer cells. I have identified a heregulin binding site in HER3, isolated a smaller piece of the receptor that is capable of binding heregulin, validated the binding site by mutagenesis and expressed non-glycosylated protein for crystallographic studies. This discovery has the potential for leading to the development of a therapeutic for breast and ovarian cancer. |
