Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module

Deborah Fass, Stephen Blacklow, Peter S. Kim, James M. Berger

Research output: Contribution to journalArticlepeer-review

Abstract

The low-density lipoprotein receptor (LDLR) is responsible for the uptake of cholesterol-containing lipoprotein particles into cells. The amino- terminal region of LDLR, which consists of seven tandemly repeated, ~40- amino-acid, cysteine-rich modules (LDL-A modules), mediates binding to lipoproteins. LDL-A modules are biologically ubiquitous domains, found in over 100 proteins in the sequence database. The structure of ligand-binding repeat 5 (LR5) of the LDLR, determined to 1.7 Å resolution by X-ray crystallography and presented here, contains a calcium ion coordinated by acidic residues that lie at the carboxy-terminal end of the domain and are conserved among LDL-A modules. Naturally occurring point mutations found in patients with the disease familial hypercholesterolaemia alter residues that directly coordinate Ca2+ or that serve as scaffolding residues of LR5.

Original languageEnglish (US)
Pages (from-to)691-693
Number of pages3
JournalNature
Volume388
Issue number6643
DOIs
StatePublished - Sep 11 1997
Externally publishedYes

ASJC Scopus subject areas

  • General

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