Structure of the LDL receptor extracellular domain at endosomal pH
G Rudenko, L Henry, K Henderson, K Ichtchenko… - Science, 2002 - science.org
G Rudenko, L Henry, K Henderson, K Ichtchenko, MS Brown, JL Goldstein, J Deisenhofer
Science, 2002•science.orgThe low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis
of lipoproteins. It discharges its ligand in the endosome at pH< 6. In the crystal structure at
pH= 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the
epidermal growth factor precursor homology domain (the modules A, B, β propeller, and C).
The modules R4 and R5, which are critical for lipoprotein binding, associate with the β
propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in …
of lipoproteins. It discharges its ligand in the endosome at pH< 6. In the crystal structure at
pH= 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the
epidermal growth factor precursor homology domain (the modules A, B, β propeller, and C).
The modules R4 and R5, which are critical for lipoprotein binding, associate with the β
propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in …
The low-density lipoprotein receptor mediates cholesterol homeostasis through endocytosis of lipoproteins. It discharges its ligand in the endosome at pH < 6. In the crystal structure at pH = 5.3, the ligand-binding domain (modules R2 to R7) folds back as an arc over the epidermal growth factor precursor homology domain (the modules A, B, β propeller, and C). The modules R4 and R5, which are critical for lipoprotein binding, associate with the β propeller via their calcium-binding loop. We propose a mechanism for lipoprotein release in the endosome whereby the β propeller functions as an alternate substrate for the ligand-binding domain, binding in a calcium-dependent way and promoting lipoprotein release.
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