Hepadnavirus envelope topology: Insertion of a loop region in the membraneand role of S in L protein translocation

A unique feature of the large hepadnavirus envelope protein (L) is its mixe d transmembrane topology, resulting from partial posttranslational transloc ation of the pre-S domain. Using protease protection analysis, we demonstra te for duck hepatitis B virus an essential role for the small envelope prot ein (S) in this process, providing the first experimental evidence for an S translocation channel. Further analysis revealed that the presumed cytopla smic loop between TM1 and TM2 in the C-terminal S domain is membrane embedd ed and protrudes to the particle surface. These data suggest that some L mo lecules form a highly folded, potentially spring-loaded topology with five membrane-spanning regions and a membrane-traversing pre-S chain.