The Carboxy-Terminal 18 Amino Acids of the Measles Virus Hemagglutinin Are Essential for Its Biological Function

The hemagglutinin (HA) glycoprotein encoded by measles virus (MV) is a type II integral membrane protein that is expressed at the infected cell surface. Genes encoding wild-type MV HA as well as two mutant HA proteins shortened at their carboxy-termini by either 18 (HAΔ18) or 223 (HAΔ223) amino acids were constructed and studied in a transient expression system in COS cells. Under nonreducing conditions, assembly of HAΔ18 into homodimers was diminished while HAΔ223 remained in a monomeric form. Hemadsorption assays revealed that neither mutant was functional at the cell surface. These studies show that the carboxy-terminal ectodomain of the HA protein is essential to its proper folding and assembly into homodimers while its carboxy-terminal 18 amino acids are essential for the hemadsorption (receptor-binding) function of the protein.