Mosaic amino acid conservation in 3D-structures of surface protein and polymerase of hepatitis B virus.
Surface protein and polymerase of hepatitis B virus provide a striking example of gene overlap. Inclusion of more coding constraints in the phylogenetic analysis forces the tree toward accepted topology. Three-dimensional protein modeling demonstrates that participation in local protein function underlies the observed mosaic patterns of amino acid conservation and variability. Conserved amino acid residues of polymerase were typically clustered at the catalytic core marked by the YMDD motif. The proposed tertiary structure of surface protein displayed the expected transmembrane helices in a 2-domain constellation. Conserved amino acids like, for instance, cysteine residues are involved in the spatial orientation of the two domains, the exposed location of the a-determinant and the dimer formation of surface protein. By means of computational alanine replacement scanning, we demonstrated that the interfaces between domains in monomeric surface protein, between the monomers in dimeric surface protein and in a capsid-surface protein complex mainly consist of relatively well-conserved amino acid residues.
van Hemert
Formijn J
FJ
Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. f.j.vanhemert@amc.uva.nl
Zaaijer
Hans L
HL
Berkhout
Ben
B
Lukashov
Vladimir V
VV
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001483:Base Sequence; D017124:Conserved Sequence; D004279:DNA, Viral / Q000235:genetics; D019281:Dimerization; D015684:Gene Products, pol / Q000737:chemistry* / Q000235:genetics; D005814:Genes, Viral; D006514:Hepatitis B Surface Antigens / Q000737:chemistry* / Q000235:genetics; D006515:Hepatitis B virus / Q000737:chemistry* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D009030:Mosaicism; D010802:Phylogeny; D011487:Protein Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D016364:Reading Frames; D013816:Thermodynamics
D004279:DNA, Viral; D015684:Gene Products, pol; D006514:Hepatitis B Surface Antigens; C066027:P protein, Hepatitis B virus