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Science 301 (5641): 1904-1908

Copyright © 2003 by the American Association for the Advancement of Science

Reprogramming Control of an Allosteric Signaling Switch Through Modular Recombination

John E. Dueber,1,3 Brian J. Yeh,2,3 Kayam Chak,3 Wendell A. Lim3*

Abstract: Many eukaryotic signaling proteins are composed of simple modular binding domains, yet they can display sophisticated behaviors such as allosteric gating and multi-input signal integration, properties essential for complex cellular circuits. To understand how such behavior can emerge from combinations of simple domains, we engineered variants of the actin regulatory protein N-WASP (neuronal Wiskott-Aldrich syndrome protein) in which the "output" domain of N-WASP was recombined with heterologous autoinhibitory "input" domains. Synthetic switch proteins were created with diverse gating behaviors in response to nonphysiological inputs. Thus, this type of modular framework can facilitate the evolution or engineering of cellular signaling circuits.

1 Program in Biological Sciences, University of California, San Francisco, CA 94143–2240, USA.
2 Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94143–2240, USA.
3 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143–2240, USA.

* To whom correspondence should be addressed. E-mail: wlim{at}itsa.ucsf.edu.

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