LIG1

Low-density lipoprotein receptor
Structure of the LDL receptor
Identifiers
Symbol	?
HGNC	6547
OMIM	606945
RefSeq	NM_000527
UniProt	P01130
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The low-density lipoprotein receptor (LDLR) is a cell surface receptor that plays a critical role in the regulation of cholesterol levels in the blood. It is primarily responsible for the endocytosis of cholesterol-rich low-density lipoprotein (LDL) particles, which are often referred to as "bad cholesterol" due to their association with atherosclerosis and cardiovascular disease.

Structure

The LDLR is a transmembrane glycoprotein composed of several distinct domains:

• The ligand-binding domain, which contains multiple repeats that bind to the apolipoprotein B-100 and apolipoprotein E present on LDL particles.
• The epidermal growth factor (EGF) precursor homology domain, which is involved in the release of LDL particles in the endosome.
• The O-linked sugar domain, which is rich in serine and threonine residues and is heavily glycosylated.
• The transmembrane domain, which anchors the receptor in the cell membrane.
• The cytoplasmic domain, which contains signals for endocytosis and interaction with the cellular machinery.

Function

The primary function of LDLR is to mediate the uptake of LDL particles from the bloodstream into cells. This process involves several steps:

1. LDL particles bind to the LDLR on the cell surface.
2. The receptor-ligand complex is internalized by endocytosis.
3. The complex is transported to the endosome, where the acidic environment causes the LDL particles to dissociate from the receptor.
4. The LDL particles are delivered to the lysosome, where they are degraded, releasing cholesterol for use by the cell.
5. The LDLR is recycled back to the cell surface to bind more LDL particles.

Clinical Significance

Mutations in the LDLR gene can lead to familial hypercholesterolemia, a genetic disorder characterized by high levels of LDL cholesterol in the blood and an increased risk of cardiovascular disease. This condition is often inherited in an autosomal dominant pattern.

Research and Therapeutics

Research into LDLR has led to the development of several therapeutic strategies aimed at lowering LDL cholesterol levels. These include:

• Statins, which increase the expression of LDLR on the cell surface.
• PCSK9 inhibitors, which prevent the degradation of LDLR, thereby increasing its availability to clear LDL from the bloodstream.

Also see

• Cholesterol metabolism
• Atherosclerosis
• Familial hypercholesterolemia
• PCSK9