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Crystal structure of two CD46 domains reveals an extended measles virus-binding surface.

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  • 1. Department of Biosciences at NOVUM, Karolinska Institute, 14157 Huddinge, Sweden.
      Authors
    • Casasnovas JM 1
    (1 author)

The EMBO Journal, 01 Jun 1999, 18(11):2911-2922
https://doi.org/10.1093/emboj/18.11.2911 PMID: 10357804 PMCID: PMC1171373

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Abstract 

Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 A resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46.

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EMBO J. 1999 Jun 1; 18(11): 2911–2922.
PMCID: PMC1171373
PMID: 10357804

Crystal structure of two CD46 domains reveals an extended measles virus-binding surface.

J M Casasnovas, M Larvie, and T Stehle
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Abstract

Measles virus is a paramyxovirus which, like other members of the family such as respiratory syncytial virus, is a major cause of morbidity and mortality worldwide. The cell surface receptor for measles virus in humans is CD46, a complement cofactor. We report here the crystal structure at 3.1 A resolution of the measles virus-binding fragment of CD46. The structure reveals the architecture and spatial arrangement of two glycosylated short consensus repeats with a pronounced interdomain bend and some flexibility at the domain interface. Amino acids involved in measles virus binding define a large, glycan-free surface that extends from the top of the first to the bottom of the second repeat. The extended virus-binding surface of CD46 differs strikingly from those reported for the human virus receptor proteins CD4 and intercellular cell adhesion molecule-1 (ICAM-1), suggesting that the CD46 structure utilizes a novel mode of virus recognition. A highly hydrophobic and protruding loop at the base of the first repeat bears a critical virus-binding residue, thereby defining an important recognition epitope. Molecules that mimic the conformation of this loop potentially could be effective anti-viral agents by preventing binding of measles virus to CD46.

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Selected References

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  • Adams EM, Brown MC, Nunge M, Krych M, Atkinson JP. Contribution of the repeating domains of membrane cofactor protein (CD46) of the complement system to ligand binding and cofactor activity. J Immunol. 1991 Nov 1;147(9):3005–3011. [Abstract] [Google Scholar]
  • Barlow PN, Steinkasserer A, Norman DG, Kieffer B, Wiles AP, Sim RB, Campbell ID. Solution structure of a pair of complement modules by nuclear magnetic resonance. J Mol Biol. 1993 Jul 5;232(1):268–284. [Abstract] [Google Scholar]
  • Bella J, Kolatkar PR, Marlor CW, Greve JM, Rossmann MG. The structure of the two amino-terminal domains of human ICAM-1 suggests how it functions as a rhinovirus receptor and as an LFA-1 integrin ligand. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4140–4145. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bergelson JM, Chan M, Solomon KR, St John NF, Lin H, Finberg RW. Decay-accelerating factor (CD55), a glycosylphosphatidylinositol-anchored complement regulatory protein, is a receptor for several echoviruses. Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6245–6248. [Europe PMC free article] [Abstract] [Google Scholar]
  • Bergelson JM, Modlin JF, Wieland-Alter W, Cunningham JA, Crowell RL, Finberg RW. Clinical coxsackievirus B isolates differ from laboratory strains in their interaction with two cell surface receptors. J Infect Dis. 1997 Mar;175(3):697–700. [Abstract] [Google Scholar]
  • Bork P, Downing AK, Kieffer B, Campbell ID. Structure and distribution of modules in extracellular proteins. Q Rev Biophys. 1996 May;29(2):119–167. [Abstract] [Google Scholar]
  • Brünger AT, Kuriyan J, Karplus M. Crystallographic R factor refinement by molecular dynamics. Science. 1987 Jan 23;235(4787):458–460. [Abstract] [Google Scholar]
  • Buchholz CJ, Koller D, Devaux P, Mumenthaler C, Schneider-Schaulies J, Braun W, Gerlier D, Cattaneo R. Mapping of the primary binding site of measles virus to its receptor CD46. J Biol Chem. 1997 Aug 29;272(35):22072–22079. [Abstract] [Google Scholar]
  • Casasnovas JM, Stehle T, Liu JH, Wang JH, Springer TA. A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4134–4139. [Europe PMC free article] [Abstract] [Google Scholar]
  • Christiansen D, Milland J, Thorley BR, McKenzie IF, Mottram PL, Purcell LJ, Loveland BE. Engineering of recombinant soluble CD46: an inhibitor of complement activation. Immunology. 1996 Mar;87(3):348–354. [Abstract] [Google Scholar]
  • Clarkson NA, Kaufman R, Lublin DM, Ward T, Pipkin PA, Minor PD, Evans DJ, Almond JW. Characterization of the echovirus 7 receptor: domains of CD55 critical for virus binding. J Virol. 1995 Sep;69(9):5497–5501. [Europe PMC free article] [Abstract] [Google Scholar]
  • Dörig RE, Marcil A, Chopra A, Richardson CD. The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell. 1993 Oct 22;75(2):295–305. [Abstract] [Google Scholar]
  • Edmonson MB, Davis JP, Hopfensperger DJ, Berg JL, Payton LA. Measles vaccination during the respiratory virus season and risk of vaccine failure. Pediatrics. 1996 Nov;98(5):905–910. [Abstract] [Google Scholar]
  • Esnouf RM. An extensively modified version of MolScript that includes greatly enhanced coloring capabilities. J Mol Graph Model. 1997 Apr;15(2):132–113. [Abstract] [Google Scholar]
  • Fingeroth JD, Weis JJ, Tedder TF, Strominger JL, Biro PA, Fearon DT. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4510–4514. [Europe PMC free article] [Abstract] [Google Scholar]
  • Garoff H, Hewson R, Opstelten DJ. Virus maturation by budding. Microbiol Mol Biol Rev. 1998 Dec;62(4):1171–1190. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hara T, Kuriyama S, Kiyohara H, Nagase Y, Matsumoto M, Seya T. Soluble forms of membrane cofactor protein (CD46, MCP) are present in plasma, tears, and seminal fluid in normal subjects. Clin Exp Immunol. 1992 Sep;89(3):490–494. [Abstract] [Google Scholar]
  • Hsu EC, Dörig RE, Sarangi F, Marcil A, Iorio C, Richardson CD. Artificial mutations and natural variations in the CD46 molecules from human and monkey cells define regions important for measles virus binding. J Virol. 1997 Aug;71(8):6144–6154. [Europe PMC free article] [Abstract] [Google Scholar]
  • Hsu EC, Sarangi F, Iorio C, Sidhu MS, Udem SA, Dillehay DL, Xu W, Rota PA, Bellini WJ, Richardson CD. A single amino acid change in the hemagglutinin protein of measles virus determines its ability to bind CD46 and reveals another receptor on marmoset B cells. J Virol. 1998 Apr;72(4):2905–2916. [Europe PMC free article] [Abstract] [Google Scholar]
  • Iwata K, Seya T, Yanagi Y, Pesando JM, Johnson PM, Okabe M, Ueda S, Ariga H, Nagasawa S. Diversity of sites for measles virus binding and for inactivation of complement C3b and C4b on membrane cofactor protein CD46. J Biol Chem. 1995 Jun 23;270(25):15148–15152. [Abstract] [Google Scholar]
  • Jones TA, Zou JY, Cowan SW, Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr A. 1991 Mar 1;47(Pt 2):110–119. [Abstract] [Google Scholar]
  • Karp CL, Wysocka M, Wahl LM, Ahearn JM, Cuomo PJ, Sherry B, Trinchieri G, Griffin DE. Mechanism of suppression of cell-mediated immunity by measles virus. Science. 1996 Jul 12;273(5272):228–231. [Abstract] [Google Scholar]
  • King SL, Kamata T, Cunningham JA, Emsley J, Liddington RC, Takada Y, Bergelson JM. Echovirus 1 interaction with the human very late antigen-2 (integrin alpha2beta1) I domain. Identification of two independent virus contact sites distinct from the metal ion-dependent adhesion site. J Biol Chem. 1997 Nov 7;272(45):28518–28522. [Abstract] [Google Scholar]
  • Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998 Jun 18;393(6686):648–659. [Abstract] [Google Scholar]
  • Liszewski MK, Post TW, Atkinson JP. Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol. 1991;9:431–455. [Abstract] [Google Scholar]
  • Lublin DM, Liszewski MK, Post TW, Arce MA, Le Beau MM, Rebentisch MB, Lemons LS, Seya T, Atkinson JP. Molecular cloning and chromosomal localization of human membrane cofactor protein (MCP). Evidence for inclusion in the multigene family of complement-regulatory proteins. J Exp Med. 1988 Jul 1;168(1):181–194. [Europe PMC free article] [Abstract] [Google Scholar]
  • Maisner A, Alvarez J, Liszewski MK, Atkinson DJ, Atkinson JP, Herrler G. The N-glycan of the SCR 2 region is essential for membrane cofactor protein (CD46) to function as a measles virus receptor. J Virol. 1996 Aug;70(8):4973–4977. [Europe PMC free article] [Abstract] [Google Scholar]
  • Manchester M, Valsamakis A, Kaufman R, Liszewski MK, Alvarez J, Atkinson JP, Lublin DM, Oldstone MB. Measles virus and C3 binding sites are distinct on membrane cofactor protein (CD46). Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2303–2307. [Europe PMC free article] [Abstract] [Google Scholar]
  • Manchester M, Gairin JE, Patterson JB, Alvarez J, Liszewski MK, Eto DS, Atkinson JP, Oldstone MB. Measles virus recognizes its receptor, CD46, via two distinct binding domains within SCR1-2. Virology. 1997 Jun 23;233(1):174–184. [Abstract] [Google Scholar]
  • McLaughlin PJ, Holland SJ, Taylor CT, Olah KS, Lewis-Jones DI, Hara T, Seya T, Johnson PM. Soluble CD46 (membrane cofactor protein, MCP) in human reproductive tract fluids. J Reprod Immunol. 1996 Oct;31(3):209–219. [Abstract] [Google Scholar]
  • Molina H, Brenner C, Jacobi S, Gorka J, Carel JC, Kinoshita T, Holers VM. Analysis of Epstein-Barr virus-binding sites on complement receptor 2 (CR2/CD21) using human-mouse chimeras and peptides. At least two distinct sites are necessary for ligand-receptor interaction. J Biol Chem. 1991 Jul 5;266(19):12173–12179. [Abstract] [Google Scholar]
  • Mumenthaler C, Schneider U, Buchholz CJ, Koller D, Braun W, Cattaneo R. A 3D model for the measles virus receptor CD46 based on homology modeling, Monte Carlo simulations, and hemagglutinin binding studies. Protein Sci. 1997 Mar;6(3):588–597. [Europe PMC free article] [Abstract] [Google Scholar]
  • Naniche D, Varior-Krishnan G, Cervoni F, Wild TF, Rossi B, Rabourdin-Combe C, Gerlier D. Human membrane cofactor protein (CD46) acts as a cellular receptor for measles virus. J Virol. 1993 Oct;67(10):6025–6032. [Europe PMC free article] [Abstract] [Google Scholar]
  • Nicholls A, Sharp KA, Honig B. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons. Proteins. 1991;11(4):281–296. [Abstract] [Google Scholar]
  • Nussbaum O, Broder CC, Moss B, Stern LB, Rozenblatt S, Berger EA. Functional and structural interactions between measles virus hemagglutinin and CD46. J Virol. 1995 Jun;69(6):3341–3349. [Europe PMC free article] [Abstract] [Google Scholar]
  • Patterson JB, Scheiflinger F, Manchester M, Yilma T, Oldstone MB. Structural and functional studies of the measles virus hemagglutinin: identification of a novel site required for CD46 interaction. Virology. 1999 Mar 30;256(1):142–151. [Abstract] [Google Scholar]
  • Rossmann MG. The canyon hypothesis. Hiding the host cell receptor attachment site on a viral surface from immune surveillance. J Biol Chem. 1989 Sep 5;264(25):14587–14590. [Abstract] [Google Scholar]
  • Ryu SE, Kwong PD, Truneh A, Porter TG, Arthos J, Rosenberg M, Dai XP, Xuong NH, Axel R, Sweet RW, et al. Crystal structure of an HIV-binding recombinant fragment of human CD4. Nature. 1990 Nov 29;348(6300):419–426. [Europe PMC free article] [Abstract] [Google Scholar]
  • Seya T, Turner JR, Atkinson JP. Purification and characterization of a membrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b. J Exp Med. 1986 Apr 1;163(4):837–855. [Europe PMC free article] [Abstract] [Google Scholar]
  • Stanley P. Chinese hamster ovary cell mutants with multiple glycosylation defects for production of glycoproteins with minimal carbohydrate heterogeneity. Mol Cell Biol. 1989 Feb;9(2):377–383. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wang JH, Yan YW, Garrett TP, Liu JH, Rodgers DW, Garlick RL, Tarr GE, Husain Y, Reinherz EL, Harrison SC. Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains. Nature. 1990 Nov 29;348(6300):411–418. [Abstract] [Google Scholar]
  • Ward T, Pipkin PA, Clarkson NA, Stone DM, Minor PD, Almond JW. Decay-accelerating factor CD55 is identified as the receptor for echovirus 7 using CELICS, a rapid immuno-focal cloning method. EMBO J. 1994 Nov 1;13(21):5070–5074. [Europe PMC free article] [Abstract] [Google Scholar]
  • Wiles AP, Shaw G, Bright J, Perczel A, Campbell ID, Barlow PN. NMR studies of a viral protein that mimics the regulators of complement activation. J Mol Biol. 1997 Sep 19;272(2):253–265. [Abstract] [Google Scholar]
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