High-density lipoprotein mediates silica nanoparticle recognition by the multiligand receptor SR-B1

TL;DR

The study shows that HDL and LDL help SR-B1 recognize silica nanoparticles through a specific amino acid cluster.

Contribution

The study reveals that a basic amino acid cluster in SR-B1 is crucial for binding HDL, LDL, and silica nanoparticles.

Findings

A basic amino acid cluster in SR-B1 is essential for binding HDL and silica nanoparticles.

SR-B1's binding to silica depends on specific interactions with HDL or LDL.

The receptor selectively binds silica but not other nanoparticles like titanium dioxide or carbon nanotubes.

Abstract

Scavenger receptor class B type 1 (SR-B1), best known as a high-density lipoprotein (HDL) receptor, is now recognized as a multi-ligand membrane receptor. In addition to HDL, SR-B1 binds low-density lipoprotein (LDL), hepatitis C virus, Gram-positive and Gram-negative bacteria, and inorganic silica particles. However, the mechanisms by which SR-B1 recognizes diverse ligands remain unclear. We previously reported that a basic amino acid cluster consisting of K151, K156, and K395 at the extracellular apex of SR-B1 is essential for charge-dependent binding to silica and is distinct from the known HDL-binding site. In this study, homology modeling of SR-B1 revealed the HDL-binding site is oriented toward the basic cluster. Site-directed mutagenesis demonstrated that this basic cluster is required for HDL and, to a lesser extent, LDL binding, which in turn promotes binding to silica nanoparticles. The selective binding of SR-B1 to silica nanoparticles, but not to titanium dioxide nanoparticles, latex nanoparticles, monosodium urate crystals, or multiwalled carbon nanotubes, depends on specific HDL–silica or LDL–silica interactions. These findings suggest that HDL, and potentially LDL, may underlie SR-B1's function as a mutiligand membrane receptor.

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