EGFR: Tale of the C-terminal tail

Authors

  • Ketan S. Gajiwala

    Corresponding author
    • Cancer Structural Biology and Oncology Medicinal Chemistry, Pfizer Worldwide Research and Development, San Diego, California
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Correspondence to: Ketan S. Gajiwala, Cancer Structural Biology and Oncology Medicinal Chemistry, Pfizer Worldwide Research and Development, 10770 Science Center Drive, San Diego, CA 92121. E-mail: ketan.gajiwala@pfizer.com.

Abstract

The carboxy terminal tail of epidermal growth factor receptor (EGFR) plays a critical role in the regulation of the enzyme activity of the kinase. There is a good structural model for the mechanism by which the C-terminal tail proximal to the kinase domain contributes to the negative regulation of the activity. Its conformation in the active state, conversely, has remained elusive due to its dynamic nature. A recently published structure of EGFR kinase domain shows the conformation of the proximal C-terminal tail in the active kinase. Analysis of this conformational state of the C-terminal tail is presented, and some of the mutagenesis data is revisited. © 2013 The Protein Society

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