Structure of the measles virus hemagglutinin bound to its cellular receptor SLAM

T Hashiguchi, T Ose, M Kubota, N Maita… - Nature structural & …, 2011 - nature.com
T Hashiguchi, T Ose, M Kubota, N Maita, J Kamishikiryo, K Maenaka, Y Yanagi
Nature structural & molecular biology, 2011nature.com
Measles virus, a major cause of childhood morbidity and mortality worldwide, predominantly
infects immune cells using signaling lymphocyte activation molecule (SLAM) as a cellular
receptor. Here we present crystal structures of measles virus hemagglutinin (MV-H), the
receptor-binding glycoprotein, in complex with SLAM. The MV-H head domain binds to a β-
sheet of the membrane-distal ectodomain of SLAM using the side of its β-propeller fold. This
is distinct from attachment proteins of other paramyxoviruses that bind receptors using the …
Abstract
Measles virus, a major cause of childhood morbidity and mortality worldwide, predominantly infects immune cells using signaling lymphocyte activation molecule (SLAM) as a cellular receptor. Here we present crystal structures of measles virus hemagglutinin (MV-H), the receptor-binding glycoprotein, in complex with SLAM. The MV-H head domain binds to a β-sheet of the membrane-distal ectodomain of SLAM using the side of its β-propeller fold. This is distinct from attachment proteins of other paramyxoviruses that bind receptors using the top of their β-propeller. The structure provides templates for antiviral drug design, an explanation for the effectiveness of the measles virus vaccine, and a model of the homophilic SLAM-SLAM interaction involved in immune modulations. Notably, the crystal structures obtained show two forms of the MV-H–SLAM tetrameric assembly (dimer of dimers), which may have implications for the mechanism of fusion triggering.
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