Structure of adenovirus type 21 knob in complex with CD46 reveals key differences in receptor contacts among species B adenoviruses
2010 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 84, no 7, 3189-3200 p.Article in journal (Refereed) Published
The complement regulation protein CD46 is the primary attachment receptor for most species B adenoviruses (Ads). However, significant variability exists in sequence and structure among species B Ads in the CD46-binding regions, correlating with differences in affinity. Here, we report a structure-function analysis of the interaction of the species B Ad21 knob with the two N-terminal repeats SCR1 and SCR2 of CD46, CD46-D2. We have determined the structures of the Ad21 knob in its unliganded form as well as in complex with CD46-D2, and we compare the interactions with those observed for the Ad11 knob-CD46-D2 complex. Surface plasmon resonance measurements demonstrate that the affinity of Ad21 knobs for CD46-D2 is 22-fold lower than that of the Ad11 knob. The superposition of the Ad21 and Ad11 knob structures in complex with CD46-D2 reveals a substantially different binding mode, providing an explanation for the weaker binding affinity of the Ad21 knob for its receptor. A critical difference in both complex structures is that a key interaction point, the DG loop, protrudes more in the Ad21 knob than in the Ad11 knob. Therefore, the protruding DG loop does not allow CD46-D2 to approach the core of the Ad21 knob as closely as in the Ad11 knob-CD46-D2 complex. In addition, the engagement of CD46-D2 induces a conformational change in the DG loop in the Ad21 knob but not in the Ad11 knob. Our results contribute to a more profound understanding of the CD46-binding mechanism of species B Ads and have relevance for the design of more efficient gene delivery vectors.
Place, publisher, year, edition, pages
American Society for Microbiology , 2010. Vol. 84, no 7, 3189-3200 p.
bone-marrow transplantation, cofactor protein CD46, cellular receptor, measles virus, maximum likelihood, crystal-structure, fiber knob, binding, cells, attachment
IdentifiersURN: urn:nbn:se:umu:diva-33398DOI: 10.1128/JVI.01964-09ISI: 000275307400005PubMedID: 20071571OAI: oai:DiVA.org:umu-33398DiVA: diva2:311734