The crystal structure of a simian Foamy Virus receptor binding domain provides clues about entry into host cells
The surface envelope glycoprotein (Env) of all retroviruses mediates virus binding to cells and fusion of the viral and cellular membranes. A structure-function relationship for the HIV Env that belongs to the Orthoretrovirus subfamily has been well established. Structural information is however largely missing for the Env of Foamy viruses (FVs), the second retroviral subfamily. FV Envs lack sequence similarity with their HIV counterpart. We present the X-ray structure of the receptor binding domain (RBD) of a simian FV Env at 2.6 [A] resolution, revealing two subdomains and an unprecedented fold. We have generated a model for the organization of the RBDs within the trimeric Env which indicates that the upper subdomain is important for stabilization of the full-length Env, and have demonstrated that residues K342, R343, R359 and R369 in the lower subdomain play key roles in the interaction of the RBD and viral particles with heparan sulfate.