Domain structure and transmembrane topology of the HBV L envelope protein. (A) Schematic representation of L consisting of the preS1, preS2 and S domains. Numbers above the domains refer to the corresponding amino acids positions. The usage of the second and third start codons located at positions 109 and 164 of L leads to synthesis of the M and S proteins, respectively, as denoted by arrows. Consensus sequences for N-glycosylation are indicated by the corresponding asparagine (N) residue. (B) Mixed topology of L at the ER membrane. Upon cotranslational membrane integration, the preS1 and preS2 domains of L are initially located on the cytosolic surface of the ER (Left). During maturation, about ~50% of the L molecules posttranslationally translocate their preS region into the ER lumen (Right). Partial cotranslational N-glycosylation occurring at N309 is indicated by (¥).