Fig. 5. Schematic representation of proposed EBV-CD21-FHOS interactions. (Left) In the unstimulated cell FHOS is in an auto-inhibited conformation in the cytoplasm. (Middle) When CD21 is engaged by one of its ligands (e.g. EBV) an intracellular signal is generated (? Rac1 activation/mechanical force) that results in release of nearby FHOS from intramolecular inhibition. FHOS unfolds and interacts with the cytoplasmic domain of CD21 via its unique C-terminal domain (CT). (Right) The exposed FH domains engage cytoskeleton associated-proteins and the FH2 domain nucleates actin leading to localized formation of actin cables. Actin clustering enables the physical relocalization of CD21 into membrane aggregates, provides an anchor for ligand bound CD21 and may regulate endocytosis.