Abstract
Representative adenoviruses from four of the five major virus subgroups have been shown to interact with the 46-kDa coxsackievirus and adenovirus receptor (CAR) that is widely expressed on many human cell types, suggesting that the ability to bind CAR may be a conserved feature of many of the ~ 50 known adenovirus serotypes. Receptor binding is a function of the distal ‘knob’ domain of the trimeric viral fiber protein. Here we review recent structural characterizations of knob, CAR and knob—CAR complexes, and we discuss how knob architecture may have evolved to accommodate opposing selective pressures to vary antigenic structure while conserving receptor binding specificity. In contrast to the hypervariability of the solvent-exposed surface of knob, the CAR receptor was found to be non-polymorphic.
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References
Anderson CW et al. (2001) Frameshift mutation in PRKDC, the gene for DNA-PKcs, in the DNA repair-defective, human, glioma-derived cell line M059J. Radiat Res 156: 2–9
Antequera F and BIRD A (1999) CpG islands as genomic footprints of promoters that are associated with replication origins. Curr Biol 9: R661–7
Antonarakis SE (2001) Chromosome 21: from sequence to applications. Curr Opin Genet Dev 11: 241–6
Bai M et al. (1993) Mutations that alter an Arg-Gly-Asp (RGD) sequence in the adenovirus type 2 penton base protein abolish its cell-rounding activity and delay virus reproduction in flat cells. J Virol 67: 5198–205
Barendswaard EC et al. (1998) Rapid and specific targeting of monoclonal antibody A33 to a colon cancer xenograft in nude mice. Int J Oncol 12: 45–53
Bell AC et al. (2001) Insulators and boundaries: versatile regulatory elements in the eukaryotic genome. Science 291: 447–50
Benihoud K et al. (1999) Adenovirus vectors for gene delivery. Curr Opin Biotechnol 10: 440–7
Bergelson JM et al. (1997) Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 275: 1320–3
Bewley MC et al. (1999) Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. Science 286: 1579–83
Boulanger PA and Puvion F (1973) Large-scale preparation of soluble adenovirus hexon, penton and fiber antigens in highly purified form. Eur J Biochem 39:37–42
Bowles KR et al. (1999) Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene. Hum Genet 105: 354–9
Chretien I et al. (1998) CTX, a Xenopus thymocyte receptor, defines a molecular family conserved throughout vertebrates. Eur J Immunol 28: 4094–104
Collins FS et al. (1998) A DNA polymorphism discovery resource for research on human genetic variation. Genome Res 8: 1229–31
Connelly MA et al. (1998) The promoters for human DNA-PKcs (PRKDC) and MCM4: divergently transcribed genes located at chromosome 8 band qll. Genomics 47: 71–83
Defer C et al. (1990) Human adenovirus-host cell interactions: comparative study with members of subgroups B and C. J Virol 64: 3661–73
Deutsch Set al. (2001) A cSNP map and database for human chromosome 21. Genome Res 11: 300–7
Dmitriev I et al. (2000) Ectodomain of coxsackievirus and adenovirus receptor genetically fused to epidermal growth factor mediates adenovirus targeting to epidermal growth factor receptor-positive cells. J Virol 74: 6875–84
Dmitriev I et al. (1998) An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol 72: 9706–13
Douglas JT et al. (1996) Targeted gene delivery by tropism-modified adenoviral vectors. Nat Biotechnol 14: 1574–8
Durmort C et al. (2001) Structure of the fiber head of Ad3, a non-CAR-binding serotype of adenovirus. Virology 285: 302–12
Freimuth P (1996) A human cell line selected for resistance to adenovirus infection has reduced levels of the virus receptor. J Virol 70: 4081–5
Freimuth P et al. (1999) Coxsackievirus and adenovirus receptor amino-terminal immunoglobulin V-related domain binds adenovirus type 2 and fiber knob from adenovirus type 12. J Virol 73: 1392–8
Gu Henneux F et al. (1997) Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle. Leukemia 11: 370–5
Guhaniyogi J and Brewer G (2001) Regulation of mRNA stability in mammalian cells. Gene 265: 11–23
Haisma HJ et al. (2000) Targeting of adenoviral vectors through a bispecific single-chain antibody. Cancer Gene Ther 7: 901–4
Hattori M et al. (2000) The DNA sequence of human chromosome 21. The chromosome 21 mapping and sequencing consortium. Nature 405: 311–9
Hautala T et al. (1998) An interaction between penton base and alpha v integrins plays a minimal role in adenovirus-mediated gene transfer to hepatocytes in vitro and in vivo. Gene Ther 5: 1259–64
Hawkins JD (1988) A survey on intron and exon lengths. Nucleic Acids Research 16: 9893–9908
Heath JK et al. (1997) The human A33 antigen is a transmembrane glycoprotein and a novel member of the immunoglobulin superfamily. Proc Natl Acad Sci USA 94: 469–74
He Y et al. (2001) Interaction of coxsackievirus B3 with the full length coxsackievirus–adenovirus receptor. Nat Struct Biol 8: 874–8
Henry LJ et al. (1994) Characterization of the knob domain of the adenovirus type 5 fiber protein expressed in Escherichia coli. J Virol 68: 5239–46
Honda T et al. (2000) The coxsackievirus-adenovirus receptor protein as a cell adhesion molecule in the developing mouse brain. Brain Res Mol Brain Res 77:19–28 HONG JS and ENGLER JA (1996) Domains required for assembly of adenovirus type 2 fiber trimers. J Virol 70: 7071–8
Hubbard SJ and Argos P (1994) Cavities and packing at protein interfaces. Protein Sci 3: 2194–206
Jackson IJ (1991) A reappraisal of non-consensus mRNA splice sites. Nucleic Acids Res 19: 3795–8
Kirby I et al. (2000) Identification of contact residues and definition of the CAR-binding site of adenovirus type 5 fiber protein. J Virol 74: 2804–13
Kirby I et al. (2001) Adenovirus type 9 fiber knob binds to the coxsackie B virusadenovirus receptor (CAR) with lower affinity than fiber knobs of other CAR-binding adenovirus serotypes. J Virol 75: 7210–4
Kwong PD et al. (1998) Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393: 648–59
Lortat-Jacob H et al. (2001) Kinetic analysis of adenovirus fiber binding to its receptor reveals an avidity mechanism for trimeric receptor-ligand interactions. J Biol Chem 276: 9009–15
Louis N et al. (1994) Cell-binding domain of adenovirus serotype 2 fiber. J Virol 68: 4104–6
Mayr GA and Freimuth P (1997) A single locus on human chromosome 21 directs the expression of a receptor for adenovirus type 2 in mouse A9 cells. J Virol 71: 412–8
Myszka DG et al. (2000) Energetics of the HIV gp120-CD4 binding reaction. Proc Natl Acad Sci USA 97: 9026–31
Nemerow GR (2000) Cell receptors involved in adenovirus entry. Virology 274: 1–4
Pereboev A et al. (2001) Phage display of adenovirus type 5 fiber knob as a tool for specific ligand selection and validation. J Virol 75: 7107–13
Persson R et al. (1985) Virus-receptor interaction in the adenovirus system: characterization of the positive cooperative binding of virions on HeLa cells. J Virol 54: 92–7
Pesole G et al. (1997) Structural and compositional features of untranslated regions of eukaryotic mRNAs. Gene 205: 95–102
Philipson L et al. (1968) Virus-receptor interaction in an adenovirus system. J Virol 2: 1064–75
Robbins PD et al. (1998) Viral vectors for gene therapy. Trends Biotechnol 16: 35–40
Robison CS and Whitt MA (2000) The membrane-proximal stem region of vesicular stomatitis virus G protein confers efficient virus assembly. J Virol 74: 2239–46
Roelvink PW et al. (1996) Comparative analysis of adenovirus fiber-cell interaction: adenovirus type 2 (Ad2) and Ad9 utilize the same cellular fiber receptor but use different binding strategies for attachment. J Virol 70: 7614–21
Roelvink PW et al. (1998) The coxsackievirus-adenovirus receptor protein can function as a cellular attachment protein for adenovirus serotypes from subgroups A, C, D, E and F. J Virol 72: 7909–15
Roelvink PW et al. (1999) Identification of a conserved receptor-binding site on the fiber proteins of CAR-recognizing adenoviridae. Science 286: 1568–71
Santis G et al. (1999) Molecular determinants of adenovirus serotype 5 fibre binding to its cellular receptor CAR. J Gen Virol 80: 1519–27
Schnell MJ et al. (1996) Foreign glycoproteins expressed from recombinant vesicular stomatitis viruses are incorporated efficiently into virus particles. Proc Natl Acad Sci USA 93: 11359–65
Seth P et al. (1994) Mechanism of enhancement of DNA expression consequent to cointernalization of a replication-deficient adenovirus and unmodified plasmid DNA. J Virol 68: 933–40
Stites SE (1997) Protein-protein interactions: interface structure, binding thermodynamics, and mutational analysis. Chem Rev 97: 1233–1250
Stouten PF et al. (1992) New triple-helical model for the shaft of the adenovirus fibre. J Mol Biol 226: 1073–84
Tainer JA et al. (1982) Determination and analysis of the 2 A-structure of copper, zinc superoxide dismutase. J Mol Biol 160: 181–217
Tomxo RP et al. (1997) HCAR and MCAR: the human and mouse cellular receptors for subgroup C adenoviruses and group B coxsackieviruses. Proc Natl Acad Sci USA 94: 3352–6
Trepel M et al. (2000) Molecular adaptors for vascular-targeted adenoviral gene delivery. Hum Gene Ther 11: 1971–81
van Oostrum J and Burnett RM (1985) Molecular composition of the adenovirus type 2 virion. J Virol 56: 439–48
van Raaij MJ et al. (2000) Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 A resolution. Structure Fold Des 8: 1147–55
van RAAIJ MJ et al. (1999) Structure of the human adenovirus serotype 2 fiber head domain at 1.5 A resolution. Virology 262: 333–43
van Raaij MJ et al. (1999) A triple p-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein. Nature 401: 935–8
Wang X and Bergelson JM (1999) Coxsackievirus and adenovirus receptor cytoplasmic and transmembrane domains are not essential for coxsackievirus and adenovirus infection. J Virol 73: 2559–62
Wickham TJ et al. (1993) Integrins a y ß 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell 73: 309–19
Wilson JM (1996) Adenoviruses as gene-delivery vehicles. N Engl J Med 334:1185–1187
Xia D et al. (1994) Crystal structure of the receptor-binding domain of adenovirus type 5 fiber protein at 1.7 A resolution. Structure 2: 1259–70
Yoshida Y et al. (1998) ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system. Oncogene 16: 2687–93
Yulug IG et al. (1995) The frequency and position of Alu repeats in cDNAs, as determined by database searching. Genomics 27: 544–8
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Howitt, J., Anderson, C.W., Freimuth, P. (2003). Adenovirus Interaction with Its Cellular Receptor CAR. In: Doerfler, W., Böhm, P. (eds) Adenoviruses: Model and Vectors in Virus-Host Interactions. Current Topics in Microbiology and Immunology, vol 272. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-05597-7_11
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DOI: https://doi.org/10.1007/978-3-662-05597-7_11
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