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Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein

Oncogene volume 20, pages 3824–3834 (2001)Cite this article

Abstract

We have developed a genetic method to determine the active orientation of dimeric transmembrane protein helices. The bovine papillomavirus E5 protein, a 44-amino acid homodimeric protein that appears to traverse membranes as a left-handed coiled-coil, transforms fibroblasts by binding and activating the platelet-derived growth factor (PDGF) β receptor. A heterologous dimerization domain was used to force E5 monomers to adopt all seven possible symmetric coiled-coil registries relative to one another within the dimer. Focus formation assays demonstrated that dimerization of the E5 protein is required for transformation and identified a single preferred orientation of the monomers. The essential glutamine residue at position 17 resided in the dimer interface in this active orientation. The active chimera formed complexes with the PDGF β receptor and induced receptor tyrosine phosphorylation. We also identified E5-like structures that underwent non-productive interactions with the receptor.

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Acknowledgements

We thank Donald Engelman, David Stern and Paul Axelsen for helpful discussions, and Jan Zulkeski for assistance in preparing this manuscript. D Mattoon was supported by a Bayer Predoctoral Fellowship. This work was supported by grants from the NIH to D DiMaio (CA37157) and from NASA to PJ Loll (NAG8-1350).

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Authors and Affiliations

  1. Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, 06510, Connecticut CT, USA

    Dawn Mattoon & Daniel DiMaio

  2. Department of Pharmacology, University of Pennsylvania School of Medicine, 3620 Hamilton Walk, Philadelphia, 19104, Pennsylvania PA, USA

    Kushol Gupta, Jeffrey Doyon & Patrick J Loll

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  1. Dawn Mattoon
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Correspondence to Daniel DiMaio.

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Mattoon, D., Gupta, K., Doyon, J. et al. Identification of the transmembrane dimer interface of the bovine papillomavirus E5 protein. Oncogene 20, 3824–3834 (2001). https://doi.org/10.1038/sj.onc.1204523

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