Receptor recognition by a hepatitis B virus reveals a novel mode of high affinity virus-receptor interaction.
The duck hepatitis B virus model system was used to elucidate the characteristics of receptor (carboxypeptidase D, gp180) interaction with polypeptides representing the receptor binding site in the preS part of the large viral surface protein. We demonstrate the pivotal role of carboxypeptidase D for virus entry and show its C-domain represents the virus attachment site, which binds preS with extraordinary affinity. Combining results from surface plasmon resonance spectroscopy and two-dimensional NMR analysis we resolved the contribution of preS sequence elements to complex stability and show that receptor binding potentially occurs in two steps. Initially, a short alpha-helix in the C-terminus of the receptor binding domain facilitates formation of a primary complex. This complex is stabilized sequentially, involving approximately 60 most randomly structured amino acids preceding the helix. Thus, hepadnaviruses exhibit a novel mechanism of high affinity receptor interaction by conserving the potential to adapt structure during binding rather than to preserve it per se. We propose that this process represents an alternative strategy to escape immune surveillance and the evolutionary pressure inherent in the compact hepadnaviral genome organization.
Urban
S
S
Zentrum für Molekulare Biologie (ZMBH), Universität Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg. s.urban@zmbh.uni-heidelberg.de
Schwarz
C
C
Marx
U C
UC
Zentgraf
H
H
Schaller
H
H
Multhaup
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D002478:Cells, Cultured; D004372:Ducks / Q000378:metabolism / Q000821:virology*; D006515:Hepatitis B virus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000821:virology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011946:Receptors, Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D012995:Solubility; D020349:Surface Plasmon Resonance; D013816:Thermodynamics
D007106:Immune Sera; D010446:Peptide Fragments; D011946:Receptors, Antigen; D011991:Receptors, Virus; C030500:hepatitis B surface antigen receptor; D002268:Carboxypeptidases; C078874:carboxypeptidase D