Crystal structure of two CD46 domains reveals an extended measles virus-binding surface

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Abstract
Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 Å resolution of the measles virus‐binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan‐free surface that extends from the top of the first to the bottom of the second repeat. The extended virus‐binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule‐1 (ICAM‐1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus‐binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti‐viral agents by preventing binding of measles virus to CD46.