title: Measles virus recognizes its receptor, CD46, via two distinct binding domains within SCR1-2.
abstract: Measles virus (MV) enters cells by attachment of the viral hemagglutinin to the major cell surface receptor CD46 (membrane cofactor protein). CD46 is a transmembrane glycoprotein whose ectodomain is largely composed of four conserved modules called short consensus repeats (SCRs). We have previously shown that MV interacts with SCR1 and SCR2 of CD46. (M. Manchester et al. (1995) Proc. Natl. Acad. Sci. USA 92, 2303-2307) Here we report mapping the MV interaction with SCR1 and SCR2 of CD46 using a combination of peptide inhibition and mutagenesis studies. By testing a series of overlapping peptides corresponding to the 126 amino acid SCR1-2 region for inhibition of MV infection, two domains were identified that interacted with MV. One domain was found within SCR1 (amino acids 37-56) and another within SCR2 (amino acids 85-104). These results were confirmed by constructing chimeras with complementary regions from structurally similar, but non-MV-binding, SCRs of decay accelerating factor (DAF; CD55). These results indicate that MV contacts at least two distinct sites within SCR1-2.
authors.affiliation: Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: M
authors.initials: M
authors.lastname: Manchester
authors.forename: J E
authors.initials: JE
authors.lastname: Gairin
authors.forename: J B
authors.initials: JB
authors.lastname: Patterson
authors.forename: J
authors.initials: J
authors.lastname: Alvarez
authors.forename: M K
authors.initials: MK
authors.lastname: Liszewski
authors.forename: D S
authors.initials: DS
authors.lastname: Eto
authors.forename: J P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: M B
authors.initials: MB
authors.lastname: Oldstone
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D016466:CHO Cells; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006801:Humans; D008459:Measles virus / Q000378:metabolism*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010449:Peptide Mapping; D014709:Vero Cells
chemical_list: D015703:Antigens, CD; C497857:CD46 protein, human; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins