Structure of the LDL receptor extracellular domain at endosomal pH

Gabby Rudenko, Lisa Henry, Keith Henderson, Konstantin Ichtchenko, Michael S. Brown, Joseph L. Goldstein, Johann Deisenhofer

Research output: Contribution to journalArticlepeer-review

350 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2353-2358
Number of pages6
Issue number5602
StatePublished - Dec 20 2002
Externally publishedYes

ASJC Scopus subject areas

  • General


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