A modified form of TurboID identifies extracellular interactions between transmembrane proteins.

Chronic dietary cholesterol activates Ral GTPases, which promote LDLR internalization and lysosomal degradation through RalBP1–REPS1 and CTSA, thereby reducing cholesterol clearance, whereas CTSA inhibition restores LDLR function and may offer a therapeutic strategy for cardiovascular disease.

The low-density lipoprotein receptor family members LRP1, LRP4 and VLDLR are entry receptors for yellow fever virus.

Hepatic inflammation-targeting pemafibrate reduces atherosclerosis in Ldlr−/− mice, supporting a role for inflammation in cardiovascular risk.

Variants in the familial hypercholesterolemia gene LDLR—the most important genetic driver of cardiovascular disease—can raise circulating low-density lipoprotein (LDL) cholesterol concentrations and increase the risk of premature atherosclerosis. ...

Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR)1. Mutations in apoB100 or in LDLR cause familial hypercholesterolaemia, an autosomal dominant disease that is characterized by a marked increase in LDL cholesterol (LDL-C) and a higher risk of cardiovascular disease2. The structure of apoB100 on LDL and its interaction with LDLR are poorly understood. Here we present the cryo-electron microscopy structures of apoB100 on LDL bound to the LDLR and a nanobody complex, which can form a C2-symmetric, higher-order complex. Using local refinement, we determined high-resolution structures of the interfaces between apoB100 and LDLR. One binding interface is formed between several small-ligand-binding modules of LDLR and a series of basic patches that are scattered along a β-belt formed by apoB100, encircling LDL. The other binding interface is formed between the β-propeller domain of LDLR and the N-terminal

ApoE2 and ApoE Christchurch variants are defective in LDLR binding, thus reducing the uptake of ApoE and associated lipid cargoes. LDLR-mediated internalization and endolysosomal delivery of ApoE lipo...

Variants in the familial hypercholesterolemia gene LDLR—the most important genetic driver of cardiovascular disease—can raise circulating low-density lipoprotein (LDL) cholesterol concentrations and i...

The low-density lipoprotein receptor family members LRP1, LRP4 and VLDLR are entry receptors for yellow fever virus.

Background: Atherosclerosis, a chronic inflammatory vascular disease driven by the accumulation of LDL-derived cholesterol on arterial walls, is the leading cause of mortality worldwide but is rare in...

ApoE2 and ApoE Christchurch variants are defective in LDLR binding, thus reducing the uptake of ApoE and associated lipid cargoes. LDLR-mediated internalization and endolysosomal delivery of ApoE lipo...

Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR)1. Mutations in apoB100 or in LDLR cause familial hypercholesterolaemia, an autosomal dominant disease that is characterized by a marked increase in LDL cholesterol (LDL-C) and a higher risk of cardiovascular disease2. The structure of apoB100 on LDL and its interaction with LDLR are poorly understood. Here we present the cryo-electron microscopy structures of apoB100 on LDL bound to the LDLR and a nanobody complex, which can form a C2-symmetric, higher-order complex. Using local refinement, we determined high-resolution structures of the interfaces between apoB100 and LDLR. One binding interface is formed between several small-ligand-binding modules of LDLR and a series of basic patches that are scattered along a β-belt formed by apoB100, encircling LDL. The other binding interface is formed between the β-propeller domain of LDLR and the N-terminal

Atherosclerosis, the leading cause of cardiovascular disease, is associated with aberrant lipid metabolism, endothelial dysfunction, and chronic inflammation, yet its early manifestations and mechanisms remain incompletely understood. As low-density lipoprotein receptor loss of function is the most common monogenic cause of atherosclerosis, we employed low-density lipoprotein receptor knockout (ldlr-/-) zebrafish to investigate the developmental origins of atherosclerotic cardiovascular disease. Single-cell RNA-sequencing under differential flow conditions in embryonic ldlr-/- zebrafish identified a population of disproportionately stressed endothelial cells marked by overexpression of heat shock protein 70 (hsp70). Hsp70 is induced in stressed endothelial cells in a flow-dependent manner in zebrafish and a subset of human endothelial cells, and its activation is associated with disrupted remodeling angiogenesis in vivo. Genetic and pharmacological studies demonstrated that hsp70 upreg