Chimeric biotin-binding papillomavirus protein

DETAILED DESCRIPTION OF THE INVENTION The first domain of the chimeric protein includes at least a portion of a papillomavirus L1 or L2 protein.
The sequence of the L1 and L2 proteins of many papillomaviruses is known, and the chimeric protein can include all or a portion of the L1 or L2 protein from any papillomavirus strain.
The second domain includes a biotin-binding polypeptide, and it can be derived from any protein known to bind biotin, many of which are known in the art (see, e.
g.
, Green et al.
, Meth.
Enzymol.
, 184, 51-67 (1990); Howard et al.
, Gene, 35, 321-31 (1985); Li et al.
, J.
Biol.
Chem.
, 267, 855-63 (1992); Saggio et al.
, Biochem.
J.
, 293, 613-16 (1993); Hiller et al.
, Biochem.
J.
, 278, 573-85 (1991)).
Examples of proteins from which the biotin-binding domain of the inventive chimeric protein, thus, include avidin, streptavidin, biotin operon repressor and biotin holoenzyme synthase, biotin carboxylase, biotin-binding phage, and the like.
Each domain of the chimeric protein contributes its respective function to the chimeric protein of the present invention.
Thus, an L1 domain is able to interact as a native L1 protein (i.
e.
, with either native L1 proteins from the same strain as the chimeric protein is derived or with other chimeric proteins) to form papillomaviruses, capsomeres, or VLPs.
The L1 protein can be further modified (e.
g.
, by deleting the residue corresponding to Cys 428 of the wild-type HPV 16 protein) to render it more able to form capsomeres than VLPs.
Such modification is preferable in some applications to ensure that the biotin-binding domain is exposed, rather than hidden in the internal region of a VLP.
Depending on how the protein is produced, however, an L1 domain can represent wild-type L1 sequence to permit the resulting chimeric protein to assemble into whole papillomaviruses or VLPs.
Moreover, an L1 domain includes sequences able to bind receptors present on target cell surfaces.
To provide these functions, where the chimeric protein includes an L1 domain, typically it includes at least the amino-terminal portion of the L1 protein