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Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor

Nature Structural Biology volume 8, pages 874–878 (2001)Cite this article

Abstract

Group B coxsackieviruses (CVB) utilize the coxsackievirus-adenovirus receptor (CAR) to recognize host cells. CAR is a membrane protein with two Ig-like extracellular domains (D1 and D2), a transmembrane domain and a cytoplasmic domain. The three-dimensional structure of coxsackievirus B3 (CVB3) in complex with full length human CAR and also with the D1D2 fragment of CAR were determined to ∼22 Å resolution using cryo-electron microscopy (cryo-EM). Pairs of transmembrane domains of CAR associate with each other in a detergent cloud that mimics a cellular plasma membrane. This is the first view of a virus–receptor interaction at this resolution that includes the transmembrane and cytoplasmic portion of the receptor. CAR binds with the distal end of domain D1 in the canyon of CVB3, similar to how other receptor molecules bind to entero- and rhinoviruses. The previously described interface of CAR with the adenovirus knob protein utilizes a side surface of D1.

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Figure 1: Stereo views of CAR bound to CVB3.
Figure 2: Orthogonal stereo views of the Cα backbone of CAR D1 and D2 (black) fit into the cryo-EM density.
Figure 3: Stereo diagrams of the ICAM-1, PVR and CAR D1 domains.
Figure 4: Footprint of domain D1 onto the CVB3 surface (left) and footprint of CVB3 onto CAR (right).

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Acknowledgements

We thank J. DeGregori at the University of Colorado Cancer Center for the hybridoma cells that we initially used to produce CAR. We thank the BNL genome sequencing group, especially B. Lade, L. Butler, K. Pellechi, J. Kieleczawa and J. Dunn, for sequence analysis of the BAC containing the CAR gene. DNA sequencing was supported in part by the Office of Biological and Environmental Research of the U.S. Department of Energy. We also thank C. Xiao, W. Zhang, S. Mukhopadhyay, B. Hébert and J. Henderson for helpful discussions, C. Towell and S. Wilder for help in preparation of the manuscript, and K. Springer for purification of the CAR D1D2 protein fragment. This work was supported by NIH grants to M.G.R., R.J.K., P.F., M.A.W. and T.S.B., and grants from the Keck Foundation and Purdue University.

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Authors and Affiliations

  1. Department of Biological Sciences, Purdue University, West Lafayette, 47907, Indiana, USA

    Yongning He, Paul R. Chipman, Carol M. Bator, Timothy S. Baker, Richard J. Kuhn & Michael G. Rossmann

  2. Biology Department, Brookhaven National Laboratory, Upton, 11973, New York, USA

    Jason Howitt, Carl W. Anderson & Paul Freimuth

  3. Department of Molecular Sciences, University of Tennessee, Memphis, 38163, Tennessee, USA

    Michael A. Whitt

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Correspondence to Michael G. Rossmann.

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He, Y., Chipman, P., Howitt, J. et al. Interaction of coxsackievirus B3 with the full length coxsackievirus-adenovirus receptor. Nat Struct Mol Biol 8, 874–878 (2001). https://doi.org/10.1038/nsb1001-874

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