Characterization of the Dimerization Domains on the Mannose-6-phosphate/Insulin-like Growth Factor II Receptor

The mannose-6-phosphate/insulin-like growth factor II (M6P/IGF2) receptor is a transmembrane protein known to sequester growth factors from the extracellular matrix. This behavior suggests a mechanism of tumor suppression. Structurally, the receptor’s extracellular region is segmented into 15 homologous repeats, which are divided further into 5 triplet domains, labelled 1-3, 4-6, 7-9, 10-12, and 13-15. What is notable about the triplets is their propensity to form dimers with triplets on a second M6P/IGF2 receptor. In fact, previous studies indicate that this protein functions optimally when dimerized. Thus, the purpose of this experiment is to characterize these domain interactions. Using a urea and dithiothreitol (DTT) disruption assay, the 7-9 triplet’s potential to dimerize was assessed. Preliminary results indicate that proximity is important for mediating interactions. The 7-9 triplet binds strongly to other 7-9 triplets on a separate M6P/IGF2 receptor; however, its association with any other triplet is not as strong comparatively.