Abstract
Adenoviruses are non-enveloped icosahedral viruses with trimeric fibre proteins protruding from their vertices. There are five known genera, from which only Mastadenoviruses have been widely studied. Apart from studying adenovirus as a biological model system and with a view to prevent or combat viral infection, there is a major interest in using adenovirus for vaccination, cancer therapy and gene therapy purposes. Adenoviruses from the Atadenovirus genus have been isolated from squamate reptile hosts, ruminants and birds and have a characteristic gene organization and capsid morphology. The carboxy-terminal virus-distal fibre head domains are likely responsible for primary receptor recognition. We determined the high-resolution crystal structure of the Snake Adenovirus 1 (SnAdV-1) fibre head using the multi-wavelength anomalous dispersion (MAD) method. Despite the absence of significant sequence homology, this Atadenovirus fibre head has the same beta-sandwich propeller topology as other adenovirus fibre heads. However, it is about half the size, mainly due to much shorter loops connecting the beta-strands. The detailed structure of the SnAdV-1 fibre head and other animal adenovirus fibre heads, together with the future identification of their natural receptors, may lead to the development of new strategies to target adenovirus vectors to cells of interest.
Highlights
Adenoviruses can cause respiratory disease, eye disease, myocarditis and gastroenteritic disease and have been studied as a molecular biology model system [1], for instance mRNA splicing was first observed in adenovirusinfected cells
Trimeric fibre proteins protrude from each of the twelve vertices. These fibre proteins have an amino-terminal virusbinding sequence, a central shaft domain [5], and a globular, carboxy-terminal fibre head domain [6, 7] involved in initial receptor-binding
The gene coding for the fibre protein is preserved in Snake Adenovirus 1 (SnAdV-1), we previously showed it encodes a 345 amino acid protein, rather than 415 as reported [26]
Summary
Adenoviruses can cause respiratory disease, eye disease, myocarditis and gastroenteritic disease (among others) and have been studied as a molecular biology model system [1], for instance mRNA splicing was first observed in adenovirusinfected cells. The structure of the SnAdV-1 fibre head domain was determined by multiwavelength anomalous diffraction up to 1.6 Aresolution, using data collected from a selenomethionine derivative crystal as described [26]. The asymmetric unit of the crystals contains one monomer of the SnAdV1 fibre head, with all the residues of the fibre head (Pro232 to Lys345) being well-resolved.
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