Functional unit of the low density lipoprotein receptor of fibroblasts: a 100,000-dalton structure with multiple binding sites.
The low density lipoprotein (apoprotein B,E) receptors of fibroblasts bind plasma lipoproteins that contain either the B (apo-B) or E (apo-E) apoproteins. These include the low density lipoproteins (LDL) containing apo-B and certain high density lipoproteins containing apo-E (e.g., the cholesterol-induced apo-E HDLc). The same receptor binds both LDL and apo-E HDLc, but the apo-E HDLc bind with much higher affinity. This higher affinity is due to the binding of apo-E HDLc to multiple receptor sites. One possible structural model for this receptor is that each apo-B,E receptor possesses a single binding site. Thus, the multiple binding of apo-E HDLc would require the recruitment of four independent receptors to bind to a single apo-E HDLc particle. A second model is that each receptor unit possesses multiple binding sites capable of binding one apo-E HDLc particle or four LDL particles. This study characterizes the apo-B,E receptors in situ in the membranes of fibroblasts by radiation inactivation. This technique allows one to determine the functional size of the receptor on the basis of the amount of radiation required to inactivate the structure. The larger the molecular size of the structure, the less ionizing radiation (generated by a linear accelerator) that will be required to abolish the receptor--ligand interaction. The functional size of the apo-B,E receptor is 106,000 Mr as determined with both LDL and apo-E HDLc binding after radiation inactivation. Furthermore, the data derived from radiation inactivation and Scatchard analysis indicate that each apo-B,E receptor has multiple binding sites and that each functional receptor unit, capable of binding one apo-E HDLc or four LDL particles, has a molecular weight of 106,000.
D001053:Apolipoproteins / Q000378:metabolism; D001665:Binding Sites; D005347:Fibroblasts; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008970:Molecular Weight; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000528:radiation effects; D011973:Receptors, LDL; D013329:Structure-Activity Relationship
D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL