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Ligand size as a determinant for catabolism by the low density lipoprotein (LDL) receptor pathway. A lattice model for LDL binding.

Chappell, D.A., Fry, G.L., Waknitz, M.A., Berns, J.J.·1991·Journal of Biological Chemistry
DOI 10.1016/s0021-9258(18)54997-8
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Abstract

Low density lipoproteins (LDL) are large (Mr = 2.5 x 10(6)) in comparison to LDL receptors (Mr = 115,000). Since most LDL receptors are clustered in coated pits, we tested the hypothesis that crowding of receptor-bound LDL particles would cause steric effects. The apparent affinity of LDL for receptors on cultured fibroblasts decreased near saturation causing concave-upward Scatchard plots. Both the higher and lower affinity components of binding were up-regulated by the cholesterol synthesis inhibitor, lovastatin, indicating that the entire binding curve was sterol-responsive. In contrast, neither component of LDL binding was present on lovastatin-treated or untreated null fibroblasts which are incapable of expressing LDL receptors. Therefore, the concave-upward Scatchard plots were entirely due to binding to LDL receptors. These results are consistent with a lattice model in which receptor-bound LDL are large enough to decrease binding to adjacent receptors. A lattice model implies that large LDL should produce steric effects at a lower receptor occupancy than should small LDL. This was tested using seven LDL fractions that differed in diameter from 20 to 27 nm. Fewer large than small LDL were bound to the cell surface at 4 degrees C and 37 degrees C, and fewer were internalized and degraded at 37 degrees C. Since large LDL bound via both apolipoprotein (apo) E and apoB100, receptor cross-linking could have caused fewer large LDL to be bound at saturation. However, when the…

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Metadata

Authors
Chappell, D. A., Fry, G. L., Waknitz, M. A., & Berns, J. J.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1991-10
Volume
266
Issue
29
Pages
19296-19302
ISSN
0021-9258
DOI
10.1016/s0021-9258(18)54997-8
Cited by
47
References
0
Language
en
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