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 character istics of receptor (carboxypeptidase D, gp180) interaction with polypeptide s representing the receptor binding site in the preS part of the large vira l surface protein, We demonstrate the pivotal role of carboxypeptidase D fo r virus entry and show its C-domain represents the virus attachment site, w hich binds preS with extraordinary affinity. Combining results from surface plasmon resonance spectroscopy and two-dimensional NMR analysis we resolve d the contribution of preS sequence elements to complex stability and show that receptor binding potentially occurs in two steps, Initially, a short a -helix in the C-terminus of the receptor binding domain facilitates formati on of a primary complex. This complex is stabilized sequentially, involving similar to 60 most randomly structured amino acids preceding the helix, Th us, hepadnaviruses exhibit a novel mechanism of high affinity receptor inte raction by conserving the potential to adapt structure during binding rathe r than to preserve it per se. We propose that this process represents an al ternative strategy to escape immune surveillance and the evolutionary press ure inherent in the compact hepadnaviral genome organization.