The LDL receptor: how acid pulls the trigger.

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.

• Authors: Natalia Beglova, Stephen C Blacklow
• Journal: Trends in biochemical sciences (Trends Biochem Sci) Vol. 30 Issue 6 Pg. 309-17 (Jun 2005) ISSN: 0968-0004 [Print] England
• PMID: 15950875 (Publication Type: Journal Article, Review)

Chemical References

• Receptors, LDL
• Epidermal Growth Factor

Topics

• Binding Sites
• Endosomes (metabolism)
• Epidermal Growth Factor (metabolism)
• Humans
• Hydrogen-Ion Concentration
• Hyperlipoproteinemia Type II (genetics, metabolism)
• Mutation
• Protein Structure, Tertiary
• Receptors, LDL (chemistry, genetics, metabolism)
• Structure-Activity Relationship