Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module.
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Fass D, Blacklow S, Kim PS, Berger JM
Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module.
Nature. 1997 Aug 14;388(6643):691-3.
- PubMed ID
- 9262405 [ View in PubMed]
- 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, approximately 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 A 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.