structure determination of adenovirus proteins


keywords: adenovirus, fibre, gene therapy, vaccination, animal adenoviruses

Adenoviruses are used as experimental vaccine, gene therapy and anti-cancer vectors. We recently solved and published the structure of the receptor-binding domain of the porcine adenovirus type 4 NADC-1 strain. This revealed a conventional head domain, which is probably not involved in receptor-binding, and a galectin domain containing two carbohydrate binding domains in tandem. The carbohydrate binding domains are organised face-to-face, contrary to expectations. Sequence comparisons and published biochemical data suggest that tandem galectin domains from other species may also show this organisation. We also solved the structure of the galectin domain in complex with several different oligosaccharides. Above a picture of the binding site, the complex with tri-N-acetyllactosamine is shown.
For two genera of adenoviruses, the Atadenoviridae and Siadenoviridae, we solved the first examples, from Snake Atadenovirus 1 and Turkey Siadenovirus 3, respectively. The knowledge of different adenovirus fibre protein structures will expand the "toolbox" of investigators looking to direct adenovirus-based vectors to specific cells.

- Menéndez-Conejero R, Nguyen TH, Singh AK, Condezo GN, Marschang RE, van Raaij MJ, San Martín C (2017) Structure of a reptilian adenovirus reveals a phage tailspike fold stabilizing a vertebrate virus capsid. Structure 25, 1562-1573.

- Nguyen TH, Ballmann MZ, Do HT, Truong HN, Benkő M, Harrach B, van Raaij MJ (2016) Crystal structure of raptor adenovirus 1 fibre head and role of the beta-hairpin in siadenovirus fibre head domains. Virol J 13, 106.

- Singh AK, Berbis MA, Ballmann MZ, Kilcoyne M, Menendez M, Nguyen TH, Joshi L, Cañada FJ, Jimenez-Barbero J, Benko M, Harrach B, van Raaij MJ (2015) Structure and Sialyllactose Binding of the Carboxy-Terminal Head Domain of the Fibre from a Siadenovirus, Turkey Adenovirus 3. PLoS One 10, e0139339.
- Nguyen TH, Vidovsky MZ, Ballmann MZ, Sanz-Gaitero M, Singh AK, Harrach B, Benko M, van Raaij MJ (2015) Crystal structure of the fibre head domain of bovine adenovirus 4, a ruminant atadenovirus. Virol J 12, 81.
- Singh AK, Menéndez-Conejero R, San Martín C, van Raaij MJ (2014) Crystal structure of the fibre head domain of the atadenovirus snake adenovirus 1. PLoS One 9, e114373.
- Pénzes JJ, Menéndez-Conejero R, Condezo GN, Ball I, Papp T, Doszpoly A, Paradela A, Pérez-Berná AJ, López-Sanz M, Nguyen TH, van Raaij MJ, Marschang RE, Harrach B, Benkő M, San Martín C (2014) Molecular characterization of a lizard adenovirus reveals the first atadenovirus with two fiber genes and the first adenovirus with either one short or three long fibers per penton. J Virol 88, 11304-11314.
- Singh AK, Menendez-Conejero R, San Martin C, van Raaij MJ (2013) Crystallization of the C-terminal domain of the fibre from snake adenovirus 1, an atadenovirus. Acta Cryst F69, 1174-1179.
- Singh AK, Ballmann MZ, Benko M, Harrach B, van Raaij MJ (2013) Crystallization of the C-terminal head domain of the fibre protein from a siadenovirus, turkey adenovirus 3. Acta Cryst F69, 1135-1139.
- Guardado-Calvo P, Muñoz EM, Llamas-Saiz AL, Fox GC, Kahn R, Curiel DT, Glasgow JN, van Raaij MJ (2010) Crystallographic structure of porcine adenovirus 4 fiber head and galectin domains. J Virol 84, 10558-10568.
- Guardado-Calvo P, Llamas-Saiz AL, Fox GC, Glasgow JN, van Raaij MJ (2009) Crystallization of the head and galectin-like domains of porcine adenovirus isolate NADC-1 fibre. Acta Cryst F65, 1149-1152.
- Guardado-Calvo P, Llamas-Saiz AL, Fox GC, Langlois P, van Raaij MJ (2007) Structure of the C-terminal head domain of the fowl adenovirus type 1 long fiber. J Gen Virol 88, 2407-2416.
- Mitraki A, Papanikolopoulou K, van Raaij MJ (2006) Natural triple beta-stranded fibrous folds. Adv. Protein Chem. 73 (Fibrous Proteins: Amyloids, Prions and Beta Proteins), 97-124.
- Guardado Calvo P, Llamas-Saiz AL, Langlois P, van Raaij MJ (2006) Crystallization of the C-terminal head domain of the avian adenovirus CELO long fibre. Acta Cryst F62, 449-452.
- Mitraki A, van Raaij MJ (2005) Folding of beta-structured fibrous proteins and self-assembling peptides. Meth. Mol Biol. 300 (Protein Nanotechnology: Protocols, Instrumentation, and Application), 125-140.
- Papanikolopoulou K, Teixeira S, Belrhali H, Forsyth VT, Mitraki A, van Raaij MJ (2004) Adenovirus fibre shaft sequences fold into the native triple beta-spiral fold when N-terminally fused to the bacteriophage T4 fibritin foldon trimerisation motif. J Mol Biol 342, 219-227.
- van Raaij MJ, Mitraki A (2004) Beta-structured viral fibres: assembly, structure and implications for materials design. Curr Opin Solid State Mater Sci 8, 151-156.
- Mitraki A, Miller S, van Raaij MJ (2002) Review: conformation and folding of novel beta-structural elements in viral fiber proteins: the triple beta-spiral and triple beta-helix. J Struct Biol 137, 236-247.
- Mitraki A, van Raaij M, Ruigrok R, Cusack S, Fernandez JF, Luckey M (2001) Structure, folding and assembly of adenovirus fibers. In: Self-assembling peptides systems in biology, medicine and engineering. A Aggeli, N Boden, S Zhang, eds, Kluwer Academic Publishers, Dordrecht, pp 221-234.
- Lortat-Jacob H, Chouin E, Cusack S, van Raaij MJ (2001) Kinetic analysis of adenovirus fiber binding to its receptor reveals an avidity mechanism for trimeric receptor-ligand interactions. J Biol Chem 276, 9009-9015.
- Leissner P, Legrand V, Schlesinger Y, Ali Hadji D, van Raaij M, Cusack S, Pavirani A, Mehtali M (2001) Influence of adenovirus fiber mutations on viral encapsidation, infectivity and in vivo tropism. Gene Ther 8, 49-57.
- van Raaij MJ, Chouin E, van der Zandt H, Bergelson JM, Cusack S (2000) Dimeric structure of the coxsackievirus and adenovirus receptor D1 domain at 1.7 A resolution. Struct Fold Des 8, 1147-1155.
- van Raaij MJ, Mitraki A, Lavigne G, Cusack S(1999) A triple beta-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein. Nature 401, 935-938.
- van Raaij MJ, Louis N, Chroboczek J, Cusack S (1999) Structure of the human adenovirus serotype 2 fiber head domain at 1.5 Angstrom resolution. Virology 232, 333-343.

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