Structure of the C-terminal head domain of the fowl adenovirus type 1 long fiber

Abstract

Avian adenovirus CELO (chicken embryo lethal orphan virus, fowl adenovirus type 1) incorporates two different homotrimeric fiber proteins extending from the same penton base: a long fiber (designated fiber 1) and a short fiber (designated fiber 2). The short fibers extend straight outwards from the viral vertices, whilst the long fibers emerge at an angle. In contrast to the short fiber, which binds an unknown avian receptor and has been shown to be essential to the invasiveness of this virus, the long fiber appears to be unnecessary for infection in birds. Both fibers contain a short N-terminal virus-binding peptide, a slender shaft domain and a globular C-terminal head domain; the head domain, by analogy with human adenoviruses, is likely to be involved mainly in receptor binding. This study reports the high-resolution crystal structure of the head domain of the long fiber, solved using single isomorphous replacement (using anomalous signal) and refined against data at 1.6 Å (0.16 nm) resolution. The C-terminal globular head domain had an anti-parallel b-sandwich fold formed by two four-stranded b-sheets with the same overall topology as human adenovirus fiber heads. The presence in the sequence of characteristic repeats N-terminal to the head domain suggests that the shaft domain contains a triple b-spiral structure. Implications of the structure for the function and stability of the avian adenovirus long fiber protein are discussed; notably, the structure suggests a different mode of binding to the coxsackievirus and adenovirus receptor from that proposed for the human adenovirus fiber heads. INTRODUCTIONAvian adenovirus or chick embryo lethal orphan (CELO) virus (also known as fowl adenovirus type 1, species Fowl adenovirus A in the genus Adenovirus of the family Adenoviridae) is a large, non-enveloped, double-stranded (ds) DNA virus (Laver et al., 1971;McCracken & Adair, 1993). The CELO virus appears to be relatively benign and has not been associated with serious pathogenicity or economic losses (Cowen et al., 1978), nor does it give rise to any evident disease state when experimentally introduced into chickens. This apparent harmlessness has sparked interest in the possibility of using CELO virus in humans as a gene therapy vector (Kelleher & Vos, 1994;Stevenson et al., 2006) or chemotherapy vehicle (Logunov et al., 2004;Shashkova et al., 2005). Studies have also been undertaken to explore its potential as a vaccination vehicle in birds (Francois et al., 2004). The 44 kb dsDNA genome of the virus is contained within a single icosahedral capsid layer (Chiocca et al., 1996). As is the case for human adenoviruses (Fabry et al., 2005;Saban et al., 2006), the capsid vertices are comprised of penton proteins and the faces of hexon proteins, with further minor proteins incorporated as stabilizers. Each penton vertex contains a pentameric penton base and two trimeric fiber proteins, the short fiber (fiber 2) and the long fiber (fiber 1), with the short fiber emerging straight from the base and the long fiber at ...

Whole-genome sequences of two turkey adenovirus types reveal the existence of two unknown lineages that merit the establishment of novel species within the genus Aviadenovirus

“…This structure revealed a triple b-spiral fold for the fiber shaft. The structures of the fiber knobs of long and short FAdV-A fibers have also been solved by X-ray crystallography (El Bakkouri et al, 2008;Guardado-Calvo et al, 2007). In this study, the main differences between the fiber structures were found in the number of repeats in the shaft region and in the loop regions of the fiber knobs.…”

“…Alignments of the repeats in the fiber shaft regions were done manually based on the triple b-spiral fold model (van Raaij et al, 1999). TAdV fiber knobs were modelled based on the FAdV-1 long fiber knob (for 1277BT fiber-1) (Guardado-Calvo et al, 2007) and FAdV-1 short fiber knob (for 1277BT fiber-2 and TAdV-4 fiber) (El Bakkouri et al, 2008).…”

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

“…The presence of the three domains, namely, the N-terminal tail, the shaft, and the C-terminal knob of the LAdV-2 fiber proteins, was predicted by manual alignment of the amino acid sequence with the model proposed by van Raaij et al (28), as shown in Fig. 3G and H. The tail region is longer for fiber1 than for fiber2 (38 and 30 residues, respectively), while the head domains contain 123 (fiber1) and 120 (fiber2) residues, predicting smaller knobs than those found in mastadenoviruses (ϳ180 aa in HAdV-2) or aviadenoviruses (over 200 aa for both fiber knobs of FAdV-1) (28,55,56). Small fiber heads seem to be a common trait in atadenoviruses: the SnAdV-1 fiber head is predicted to have 111 residues (57), and the OAdV-7 fiber head is also smaller, as observed by EM (16).…”

“…The FAdV-1 long fiber, which is dispensable for infection in chicken cells, is required for infection of CAR-expressing mammalian cells, although direct binding has not been proved (55,61). No receptor has been identified for the short fibers in either HAdV-40 or -41 or FAdV-1.…”

Crystallographic Structure of Porcine Adenovirus Type 4 Fiber Head and Galectin Domains

“…Animal adenoviruses are of particular interest, as they may be less immunogenic to humans and may have novel receptor-binding properties. Recently, canine and fowl adenovirus fiber heads have been crystallized and their structures determined (44,17,18,13).…”