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Adenovirus type 11 binding alters the conformation of its receptor CD46

Abstract

Adenoviruses (Ads) are important human pathogens and valuable gene delivery vehicles. We report here the crystal structure of the species B Ad11 knob complexed with the Ad11-binding region of its receptor CD46. The conformation of bound CD46 differs profoundly from its unbound state, with the bent surface structure straightened into an elongated rod. This mechanism of interaction is likely to be conserved among many pathogens that target CD46 or related molecules.

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Figure 1: Structure of the Ad11 knob complexed with CD46 SCR1-SCR2.
Figure 2: Interaction between the Ad11 knob and CD46 SCR1-SCR2.

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Acknowledgements

We thank U. Scheu for CD46 purification, M. Hulko for affinity measurements and the staff at Swiss Light Source beamline X06SA for assistance with data collection. We acknowledge support from the Deutsche Forschungsgemeinschaft (STE-1463, SFB-685) and the Swedish Research Council (529-2003-6008 and 521-2004-6174).

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Authors

Contributions

N.A. and T.S. conceived the experiments and supervised the project, B.D.P., D.M.R. and T.S. carried out the structural studies, J.M.C. and T.S. designed the expression and purification of CD46 fragments, M.M. and N.A. carried out the binding assays, Y.-F.M. provided Ad knob constructs, expressed protein and contributed expertise on biological properties of Ad knobs, and B.D.P., N.A. and T.S. wrote the manuscript.

Corresponding author

Correspondence to Thilo Stehle.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Binding of CD46 SCR1-SCR2 and SCR1-SCR4 fragments to Ad11 knob. (PDF 1882 kb)

Supplementary Fig. 2

Binding surface for Ad11 knob on CD46. (PDF 616 kb)

Supplementary Fig. 3

Sequences of Ad11 knob and CD46 SCR1-SCR2. (PDF 528 kb)

Supplementary Table 1

Data collection and refinement statistics. (PDF 73 kb)

Supplementary Methods (PDF 116 kb)

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Persson, B., Reiter, D., Marttila, M. et al. Adenovirus type 11 binding alters the conformation of its receptor CD46. Nat Struct Mol Biol 14, 164–166 (2007). https://doi.org/10.1038/nsmb1190

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