Structure of the LDL receptor extracellular domain at endosomal pH

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

Research output: Contribution to journalArticle

326 Citations (Scopus)

Abstract

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
JournalScience
Volume298
Issue number5602
DOIs
StatePublished - Dec 20 2002
Externally publishedYes

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LDL Receptors
Lipoproteins
Endosomes
Ligands
Calcium
Endocytosis
Homeostasis
Cholesterol

ASJC Scopus subject areas

  • General

Cite this

Rudenko, G., Henry, L., Henderson, K., Ichtchenko, K., Brown, M. S., Goldstein, J. L., & Deisenhofer, J. (2002). Structure of the LDL receptor extracellular domain at endosomal pH. Science, 298(5602), 2353-2358. https://doi.org/10.1126/science.1078124

Structure of the LDL receptor extracellular domain at endosomal pH. / Rudenko, Gabrielle; Henry, Lisa; Henderson, Keith; Ichtchenko, Konstantin; Brown, Michael S.; Goldstein, Joseph L.; Deisenhofer, Johann.

In: Science, Vol. 298, No. 5602, 20.12.2002, p. 2353-2358.

Research output: Contribution to journalArticle

Rudenko, G, Henry, L, Henderson, K, Ichtchenko, K, Brown, MS, Goldstein, JL & Deisenhofer, J 2002, 'Structure of the LDL receptor extracellular domain at endosomal pH', Science, vol. 298, no. 5602, pp. 2353-2358. https://doi.org/10.1126/science.1078124
Rudenko G, Henry L, Henderson K, Ichtchenko K, Brown MS, Goldstein JL et al. Structure of the LDL receptor extracellular domain at endosomal pH. Science. 2002 Dec 20;298(5602):2353-2358. https://doi.org/10.1126/science.1078124
Rudenko, Gabrielle ; Henry, Lisa ; Henderson, Keith ; Ichtchenko, Konstantin ; Brown, Michael S. ; Goldstein, Joseph L. ; Deisenhofer, Johann. / Structure of the LDL receptor extracellular domain at endosomal pH. In: Science. 2002 ; Vol. 298, No. 5602. pp. 2353-2358.
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