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Science 290 (5491): 523-527

Copyright © 2000 by the American Association for the Advancement of Science

Two-Amino Acid Molecular Switch in an Epithelial Morphogen That Regulates Binding to Two Distinct Receptors

Minhong Yan,1* Li-Chong Wang,1* Sarah G. Hymowitz,2 Sarah Schilbach,3 James Lee,3 Audrey Goddard,3 Abraham M. de Vos,2 Wei-Qiang Gao,1 Vishva M. Dixit1dagger

Ectodysplasin, a member of the tumor necrosis factor family, is encoded by the anhidrotic ectodermal dysplasia (EDA) gene. Mutations in EDA give rise to a clinical syndrome characterized by loss of hair, sweat glands, and teeth. EDA-A1 and EDA-A2 are two isoforms of ectodysplasin that differ only by an insertion of two amino acids. This insertion functions to determine receptor binding specificity, such that EDA-A1 binds only the receptor EDAR, whereas EDA-A2 binds only the related, but distinct, X-linked ectodysplasin-A2 receptor (XEDAR). In situ binding and organ culture studies indicate that EDA-A1 and EDA-A2 are differentially expressed and play a role in epidermal morphogenesis.

1 Department of Molecular Oncology,
2 Department of Protein Engineering,
3 Department of Molecular Biology, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: dixit{at}gene.com

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