Figure 6. Model of HIV internalization by langerin.

(A) Glycosylated structure of HIV-1 envelope (env, gray) (Constructed based on PDB ID: 5FYJ and 6ULC) bound to the langerin trimer complex. Branches of the high-mannose oligosaccharide interacting with the primary (yellow) and secondary (pink) carbohydrate-binding sites. The broken square indicates the position of the close-up view on the right. (B) Schematics of HIV internalization by langerin. The inset on the top shows an overview of antigen processing within a Langerhans cell. Viruses are captured by langerin, internalized into a Birbeck granule, and degraded by the autophagic system. The red square indicates the viral entry process described in the lower panels. The high-mannose oligosaccharide on HIV-1 env first binds to the primary carbohydrate-binding site, and one of the branches of the oligo-mannose weakly interacts with the secondary binding site. The flexible neck region allows docking of the loop 258–263 of an adjacent trimer into the secondary carbohydrate-binding cleft, reinforcing the binding of the oligo-mannose. As the elastic neck regions straighten, the plasma membrane is deformed into a lamellar invagination, which internalizes the virus.