Question

Protein misfolding can be an aspect of several different human disorders, including cystic fibrosis, Alzheimer's disease, and atherosclerosis. Many times, the misfolded protein is a membrane protein. In fact, a type of diabetes insipidus results from a mutation in the G-protein-coupled vasopressin 2 receptor that prevents the protein from making it to the cell membrane! Describe how this type of receptor would normally get targeted to the membrane (from the beginning of translation) and then propose one mechanism by which the mutation could cause a lack of proper targeting.?

Answer 1

G protein-coupled receptors (GPCR) comprise the largest family of drug targets. This is not surprising as many signaling systems rely on this class of receptor to convert external and internal stimuli to intracellular responses. As is the case with other membrane proteins, GPCRs are subjected to a stringent quality control mechanism at the endoplasmic reticulum, which ensures that only correctly folded proteins enter the secretory pathway. Because of this quality control system, point mutations resulting in protein sequence variations may result in the production of misfolded and disease-causing proteins that are unable to reach their functional destinations in the cell.