Research Article

Structure of the LDL Receptor Extracellular Domain at Endosomal pH

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Science  20 Dec 2002:
Vol. 298, Issue 5602, pp. 2353-2358
DOI: 10.1126/science.1078124

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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.

  • * Present address: New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.

  • To whom correspondence should be addressed. E-mail: Johann.Deisenhofer{at}

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