THE TOPOLOGY OF THE S-PROTEIN IN THE YEAST-DERIVED HEPATITIS-B SURFACE-ANTIGEN PARTICLES

Hepatitis B surface antigen particles are highly immunogenic and have been shown to provide a suitable support for the presentation of forei gn epitopes. More information about the topology of their constitutive protein, the S (small envelope) protein, is a prerequisite to any rat ional attempt to replace region of this protein with foreign epitopes without modifying the assembly of the particle. The topology of the S protein within the lipid membrane was investigated here by combining e xtensive proteolysis of the external protein domains with proteinase K and (FTIR-ATR). The proteolytic hydrolysis of the S protein and the i dentification of the digestion products allowed characterization of th e membrane-protected regions of the protein. FTIR spectra of the diges ted hepatitis B particles revealed that the peptides associated with t he particles are rich in cu-helix structure. The kinetic of H-2/H exch ange provided evidence that a large fraction of the native S protein i s poorly accessible to the aqueous medium.