The low-density lipoprotein (LDL) receptor is an important protein in human function. LDL receptor is the main protein that binds and carries cholesterol to maintain homeostasis in mammalian cells. In human plasma, it is also the most abundant cholesterol-carrying lipoprotein (Goldstein and Brown, 1987). It plays a major role in the development of atherosclerosis, a chronic disease caused by the accumulation of LDL-cholesterol in the blood. The LDL receptor is also the main protein that is defective in individuals with familial hypercholesterolaemia, a genetic disease characterized by high levels of LDL cholesterol (Saha, et al., 2001). Individuals with familial hypercholesterolaemia generally develop cardiovascular complications and experience
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This involves four steps. The first step occurs at the cell surface in which the receptor binds to lipoproteins (Zhao and Michaely, 2011) Next, the bound lipoproteins are internalized through clathrin coated pits. This is necessary for the LDL receptor to carry the bound LDL into the cells as these pits are the entrance into the cell (Goldstein and Brown, 1987). Soon after the clathrin coated pits form, they invaginate to for coated endocytic vesicles. The vesicles quickly shed their coats and fuse together with another becoming endosomes. Once in the endosomes, the LDL is released from the receptor due to the acidic pH. The acidic pH causes a conformational change in the LDL receptor which causes the interaction between the LDL receptor and the LDL (Zhao and Michaely, 2011). At a neutral pH the LDL receptor is in an extended conformation and the acidic pH causes it to change to a compact conformation. One the LDL is released, it is degraded in lysosomes and the receptors are then sent back to the cell surface where they are recycled in order to repeat the process. This process and function of the LDL receptor occurs primarily in the …show more content…
The domain is located outside of the plasma membrane and has little function in the LDL receptor (Goldstein and Brown, 1984). However, it is believed that this domain's main function is to extend the LDL receptor to allow the binding sites of the first domain, the ligand binding domain, to stick out of the membrane, which allows for increased ease of signal transduction (Jeon and Shipley, 2000). In addition to being rich in O-linked oligosaccharides, this domain is also rich in serine and threonine. Eighteen of the forty-eight amino acids that make up the receptor are serine and threonine resides (Goldstein and Brown, 1984). These resides contain carbohydrate molecules that are attached via O-glycosidic
This involves four steps. The first step occurs at the cell surface in which the receptor binds to lipoproteins (Zhao and Michaely, 2011) Next, the bound lipoproteins are internalized through clathrin coated pits. This is necessary for the LDL receptor to carry the bound LDL into the cells as these pits are the entrance into the cell (Goldstein and Brown, 1987). Soon after the clathrin coated pits form, they invaginate to for coated endocytic vesicles. The vesicles quickly shed their coats and fuse together with another becoming endosomes. Once in the endosomes, the LDL is released from the receptor due to the acidic pH. The acidic pH causes a conformational change in the LDL receptor which causes the interaction between the LDL receptor and the LDL (Zhao and Michaely, 2011). At a neutral pH the LDL receptor is in an extended conformation and the acidic pH causes it to change to a compact conformation. One the LDL is released, it is degraded in lysosomes and the receptors are then sent back to the cell surface where they are recycled in order to repeat the process. This process and function of the LDL receptor occurs primarily in the …show more content…
The domain is located outside of the plasma membrane and has little function in the LDL receptor (Goldstein and Brown, 1984). However, it is believed that this domain's main function is to extend the LDL receptor to allow the binding sites of the first domain, the ligand binding domain, to stick out of the membrane, which allows for increased ease of signal transduction (Jeon and Shipley, 2000). In addition to being rich in O-linked oligosaccharides, this domain is also rich in serine and threonine. Eighteen of the forty-eight amino acids that make up the receptor are serine and threonine resides (Goldstein and Brown, 1984). These resides contain carbohydrate molecules that are attached via O-glycosidic