Features of hepadnavirus large envelope proteins. (A) A representation for HBV of the three envelope proteins, L, M, and S. The domains pre-S1, pre-S2, and S are indicated. The numbers refer to the amino acid positions for genotype A, serotype adw2 (NCBI protein database accession number AAK58874.1). Coloring is as described in the legend for panel B. (B) Alignment of the amino acid sequences for the large envelope proteins of HBV and DHBV (NCBI protein database accession number AAA62820.1). The alignment was obtained after three iterations of PSI-BLAST. Aligned regions, indicated in uppercase letters, span residue 23 of the human sequence (beginning with GFFP) to residue 271 (ending with LLVL). In lowercase letters are the regions before and after these positions that could not be meaningfully aligned. Transmembrane helices predicted using the program TMHMM (18) are shown in pink. The predicted third transmembrane helices of the two sequences were then manually aligned. Note that HBV has a fourth transmembrane domain. Previous reports have made somewhat different predictions for the number of such domains (7, 11, 12). Identical amino acids are marked under the alignment with asterisks, highly similar residues with colons (e.g., R/K or V/I pairs), and similar residues with periods (e.g., two hydrophobic residues or two hydrophilic residues). The amino acids of the predicted RBDs of HBV and DHBV are underlined. For DHBV, this region is overlapped by what is considered to be the binding site for CPD and may include an alpha-helical region (37). Indicated in yellow are the putative TLMs: two for DHBV and one for HBV (29). Indicated in blue is the region of HBV pre-S1 that has been implicated in attachment (14). The corresponding region of DHBV would be amino acids 2 to 41 (ending GKFP) (36). Indicated in green is the so-called matrix domain of HBV (positions 98 to 124) (3). The limits of HBV pre-S1, pre-S2, and S are indicated by arrows.