Cell-binding domain of adenovirus serotype 2 fiber

Abstract

The adenovirus fiber appears as a long, thin projection terminated by a knob (head). The fiber consists of a trimeric protein whose head domain is thought to interact with cell receptors. The head part (amino acids 388 to 582) of adenovirus type 2 fiber was produced in a baculovirus expression system. The purified protein was shown to cross-link into trimers. It was very resistant to proteolytic attack and seemed to attain a high degree of compactness. The head domain efficiently inhibited attachment of adenovirus to receptors on the surface of HeLa cells, thereby confirming the hypothesis that the head domain interacts with viral receptors.One of the major constituents of the adenovirus outer capsid is an elongated structure, the fiber, protruding from each of the twelve fivefold vertices of the icosahedral virion (for a review, see reference 10). These fibers play a crucial role in adenovirus infection by attaching the virus to specific receptors on the cell surface (2,13,18).The adenovirus type 2 (Ad2) fiber appears as a long, thin projection terminated by a knob (head) (15,16) and is a trimer of three identical subunits (17). Ad2 fiber polypeptide (582 amino acids) can be divided into three regions (4): a short amino-terminal tail region, a shaft consisting of repeating units each of approximately 15 amino acids whose relative hydrophobicities rather than strict identities tend to be conserved, and a carboxy-terminal part of about 180 residues.

Inhibition of cell adhesion to the virus by synthetic peptides of fiber knob of human adenovirus serotypes 2 and 3 and virus neutralisation by anti-peptide antibodies

“…The first step in the interaction of the adenovirus with a permissive cell is the attachment of the virus, via the head domain of the fiber, to a primary cell plasma membrane receptor (Bai et al, 1993;Mathias et al, 1994;Louis et al, 1994;Di Guilmi et al, 1995) and via the RGD sequence motif of the penton base to a second receptor. Despite the extensive study of the fiber there are some questions, so it is not known which sequences of the fiber knob participate in the virus attachment.…”

Adenovirus 3 penton dodecahedron exhibits structural changes of the base on fibre binding.

“…This observation has opened up interesting possibilities not only for gene therapy (Fender et al, 1997), but also for the study of the penton base-fibre interaction. Infection by adenoviruses is unusual in that two cell recognition sites appear to be involved (Philipson et al, 1968;Wickham et al, 1993;Cuzange et al, 1994;Henry et al, 1994;Louis et al, 1994). The first, on the knob of the fibre, recognizes a cell receptor.…”

Genetic retargeting of adenovirus vectors: functionality of targeting ligands and their influence on virus viability

“…On the virus capsid, the fiber is linked noncovalently to the penton base capsomer at the vertexes of the virus icosahedron [8]. The N-terminal tail of the fiber is the domain which mediates binding to the penton base and carries the fiber nuclear localization signal KRAR [9], while the Cterminal domain of the fiber forms a globular structure (the 'knob') which is responsible for fiber trimerization and receptor binding [10,11]. The central domain of the fiber, called the shaft, is composed of 22 repeats of a conserved, 15 amino acid motif.…”