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PubMed · 15950875

The LDL receptor: how acid pulls the trigger.

Natalia Beglova·Stephen C Blacklow
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Abstract

The low-density lipoprotein receptor normally carries lipoprotein particles into cells, and releases them upon delivery to the low pH milieu of the endosome. Recent structural and functional studies of the receptor, combined with the plethora of prior knowledge about normal receptor function and the effects of disease-associated mutations that cause familial hypercholesterolemia, reveal a detailed molecular model for how the acidic environment of the endosome triggers the release of bound lipoprotein particles. Remarkably, the receptor dynamically interconverts between open (ligand-active) and closed (ligand-inactive) conformations in response to pH, relying on a specific arrangement of fixed and flexible interdomain connections to facilitate efficient binding and release of its lipoprotein ligands.

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Binding SitesEndosomesEpidermal Growth FactorHumansHydrogen-Ion ConcentrationHyperlipoproteinemia Type IIMutationProtein Structure, TertiaryReceptors, LDLStructure-Activity RelationshipJournal ArticleReview

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BibTeXRIS

Natalia Beglova, Stephen C Blacklow. 2005. The LDL receptor: how acid pulls the trigger.. https://doi.org/10.1016/j.tibs.2005.03.007

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