Figure 2

Oxysterols such as 25-hydroxycholesterol bind to integrin αvβ3 at site II, which is distinct from the primary RGD-binding site. (A) A full-length integrin αvβ3 (secondary structure representation) bound to an oxysterol (licorice representation) at site II is shown embedded in the lipid bilayer consisting of POPC and cholesterol. The αv and β3 subunits of integrin are shown in light green and pink colors, respectively. Site II, denoted by an arrow, is 6 Å away from the primary “RGD” binding site, where extracellular matrix proteins such as fibronectin are known to bind. The polar headgroups of the lipid bilayer are represented as the vdW surface model (nitrogen in blue, phosphate in orange, and oxygen in red colors), and the alkyl chains are shown as a transparent stick model. The extracellular domain is embedded in the bilayer through two transmembrane helices. (B) Site II is formed at the interface between the β-propeller domain (light green) of the αv subunit and the βI domain (light pink) of the β3 subunit. Critical binding site residues from each domain are shown in respective darker colors. The specificity-determining loop (SDL) connects site II with the primary “RGD” binding site.