Nucleic Acids Research Advance Access originally published online on September 18, 2007
Nucleic Acids Research 2007 35(19):6357-6366; doi:10.1093/nar/gkm692
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Nucleic Acids Research, 2007, Vol. 35, No. 19 6357-6366
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Molecular Biology |
The role of peptide motifs in the evolution of a protein network
1Department of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, 2CREST, Japan Science and Technology Corporation (JST), Kawaguchi Center Building 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, 3Laboratory of Gene Biodynamics, Graduate School of Biostudies, Kyoto University, Oiwake-cho, Kitashirakawa, Sakyo-ku, Kyoto, 606-8502 and 4ICORP, JST, Kawaguchi Center Building 4-1-8, Honcho, Kawaguchi-shi, Saitama 332-0012, Japan
*To whom correspondence should be addressed. Tel: +81 3 3570 0489; Fax: +81 3 3570 0461; Email: kshiba{at}jfcr.or.jp Correspondence may also be addressed to Hirohide Saito. Tel: +81 75 753 3997; Fax: +81 75 753 3996; Email: saito{at}lif.kyoto-u.ac.jp
Received April 17, 2007. Revised August 21, 2007. Accepted August 22, 2007.
Naturally occurring proteins in cellular networks often share peptide motifs. These motifs have been known to play a pivotal role in protein interactions among the components of a network. However, it remains unknown how these motifs have contributed to the evolution of the protein network. Here we addressed this issue by a synthetic biology approach. Through the motif programming method, we have constructed an artificial protein library by mixing four peptide motifs shared among the Bcl-2 family proteins that positively or negatively regulate the apoptosis networks. We found one strong pro-apoptotic protein, d29, and two proteins having moderate, but unambiguous anti-apoptotic functions, a10 and d16, from the 28 tested clones. Thus both the pro- and anti-apoptotic modulators were present in the library, demonstrating that functional proteins with opposing effects can emerge from a single pool prepared from common motifs. Motif programming studies have exhibited that the annotated function of the motifs were significantly influenced by the context that the motifs embedded. The results further revealed that reshuffling of a set of motifs realized the promiscuous state of protein, from which disparate functions could emerge. Our finding suggests that motifs contributed to the plastic evolvability of the protein network.