MAPPING OF THE PRIMARY BINDING-SITE OF MEASLES-VIRUS TO ITS RECEPTOR CD46

The measles virus (Mn) hemagglutinin binds to the complement control p rotein (CCP) CD46 primarily through the two external modules, CCP-I an d -II, To define the residues involved in binding, 40 amino acids pred icted to be solvent-exposed on the CCP-I-II module surface were change d to either alanine or serine, Altered proteins were expressed on the cell surface, and their abilities to bind purified PUN particles, a so luble form of hemagglutinin (sH) and nine CD46-specific antibodies com peting to different levels with sH attachment, were measured, All prot eins retained, at least in part, PUN and sH binding, but some complete ly lost binding to certain antibodies. Amino acids essential for bindi ng of antibodies weakly or moderately competing with sH attachment are situated in the membrane-distal tip of CCP-I, whereas residues involv ed in binding of strongly sH competing antibodies cluster in the cente r of CCP-I (Arg-25, Asp-27) or in CCP-II (Arg-69, Asp-70). Both cluste rs face the same side of CCP-I II and map close to amino acid exchange s impairing sH binding (E11A, R29A, P39A, and D70A) or MV binding (D70 A and E84A) and to a six-amino acid loop, previously shown to be neces sary for sH binding.