TY - JOUR
T1 - Measles virus recognizes its receptor, CD46, via two distinct binding domains within SCR1-2
AU - Manchester, Marianne
AU - Gairin, Jean Edouard
AU - Patterson, John B.
AU - Alvarez, Jose
AU - Liszewski, M. Kathryn
AU - Eto, Danelle S.
AU - Atkinson, John P.
AU - Oldstone, Michael B.A.
N1 - Funding Information:
We are grateful to Tianwei Lin for generating the computer model of SCR1-2 and for helpful discussions. We acknowledge Dr. Doug Lublin for the gift of M75 antibody, Cytomed, Inc. (Cambridge, MA) for the gift of sCD46, Lia Daniels for technical assistance, and Dr. H. Mazarguil, Institut de Pharmacologie et de Biologie Structurale, CNRS, Toulouse, for peptide synthesis. We also thank Drs. Ira Schulman, Denise Nani-che, and members of the Oldstone laboratory for helpful discussions. This work was supported by Grant AI-39466 from the National Institutes of Health, NIMH training Grant MH19185 (J.P.), and by a grant from the World Health Organization (M.M.).
PY - 1997/6/23
Y1 - 1997/6/23
N2 - 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 (amine 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 SCRI-2.
AB - 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 (amine 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 SCRI-2.
UR - http://www.scopus.com/inward/record.url?scp=0030751205&partnerID=8YFLogxK
U2 - 10.1006/viro.1997.8581
DO - 10.1006/viro.1997.8581
M3 - Article
C2 - 9201227
AN - SCOPUS:0030751205
SN - 0042-6822
VL - 233
SP - 174
EP - 184
JO - Virology
JF - Virology
IS - 1
ER -