Structure of the measles virus hemagglutinin bound to the CD46 receptor.
The highly contagious measles virus infects millions of individuals worldwide, causing serious disease in children of developing countries. Infection is initiated by attachment of the measles virus hemagglutinin (MV-H), a glycoprotein anchored to the virus envelope, to the host cell receptors CD46 or signaling lymphocyte activation molecule (SLAM). Here we report the crystal structure of MV-H in complex with a CD46 protein spanning the two N-terminal domains. A unique groove at the side of the MV-H beta-propeller domain, which is absent in homologous paramyxovirus attachment proteins, engages residues in both CD46 domains. Key contacts involve a protruding loop in the N-terminal CD46 domain that carries two sequential proline residues (PP motif) and penetrates deeply into a hydrophobic socket in MV-H. We identify a similar PP motif in SLAM, defining a common measles virus recognition epitope in the CD46 and SLAM receptor proteins.
Santiago
César
C
Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, Campus Universidad Autónoma, Madrid, Spain.
Celma
María L
ML
Stehle
Thilo
T
Casasnovas
José M
JM
D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D003460:Crystallization; D006389:Hemagglutinins, Viral / Q000737:chemistry* / Q000378:metabolism; D008459:Measles virus / Q000737:chemistry*; D051916:Membrane Cofactor Protein / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1
D015703:Antigens, CD; D006389:Hemagglutinins, Viral; D051916:Membrane Cofactor Protein; D011956:Receptors, Cell Surface; C032397:hemagglutinin protein G, measles virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1