Entero virus 71 (EV71) causes hand,foot,and mouth disease (HFMD) and occasionally leads to severe neurological complications and even death.Scavenger receptor class B member 2 (SCARB2) is a functional receptor for EV71,that mediates viral attachment,intealization,and uncoating.However,the exact binding site of EV71 on SCARB2 is unknown.In this study,we generated a monoclonal antibody (mAb) that binds to human but not mouse SCARB2.It is named JL2,and it can effectively inhibit EV71 infection of target cells.Using a set of chimeras of human and mouse SCARB2,we identified that the region containing residues 77-113 of human SCARB2 contributes significantly to JL2 binding.The structure of the SCARB2-JL2 complex revealed that JL2 binds to the apical region of SCARB2 involving o-helices 2,5,and 14.Our results provide new insights into the potential binding sites for EV71 on SCARB2 and the molecular mechanism of EV71 entry.