Publication Date:
2003-09-27
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Dueber, John E -- Yeh, Brian J -- Chak, Kayam -- Lim, Wendell A -- New York, N.Y. -- Science. 2003 Sep 26;301(5641):1904-8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Program in Biological Sciences, University of California, San Francisco, CA 94143-2240, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14512628" target="_blank"〉PubMed〈/a〉
Keywords:
Actins/metabolism
;
Allosteric Regulation
;
Amino Acid Motifs
;
Animals
;
Combinatorial Chemistry Techniques
;
Evolution, Molecular
;
Ligands
;
Male
;
Nerve Tissue Proteins/*chemistry/genetics/*metabolism
;
Oocytes/metabolism
;
Peptide Library
;
Protein Engineering
;
Protein Structure, Tertiary
;
Recombinant Fusion Proteins/chemistry/metabolism
;
Recombination, Genetic
;
*Signal Transduction
;
Wiskott-Aldrich Syndrome Protein, Neuronal
;
Xenopus
;
cdc42 GTP-Binding Protein/metabolism
;
src Homology Domains
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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