Structure of Semliki Forest virus in complex with its receptor VLDLR

Semliki Forest virus (SFV) is an alphavirus that uses the very-low-density lipoprotein receptor (VLDLR) as a receptor during infection of its vertebrate hosts and insect vectors. Herein, we used cryoelectron microscopy to study the structure of SFV in complex with VLDLR. We found that VLDLR binds multiple E1-DIII sites of SFV through its membrane-distal LDLR class A (LA) repeats. Among the LA repeats of the VLDLR, LA3 has the best binding affinity to SFV. The high-resolution structure shows that LA3 binds SFV E1-DIII through a small surface area of 378 A2, with the main interactions at the interface involving salt bridges. Compared with the binding of single LA3s, consecutive LA repeats around LA3 promote syn-ergistic binding to SFV, during which the LAs undergo a rotation, allowing simultaneous key interactions at multiple E1-DIII sites on the virion and enabling the binding of VLDLRs from divergent host species to SFV.

Automated summary

It is discovered that Semliki Forest virus (SFV) uses the very-low-density lipoprotein receptor (VLDLR) as a receptor during infection. The VLDLR binds multiple E1-DIII sites on SFV, with LA3 having the strongest binding affinity. The high-resolution structure shows that LA3 binds SFV E1-DIII through a small surface area, facilitating the binding of VLDLRs from different host species to SFV.