A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering
The versatile coiled-coil protein motif is widely used to induce and control macromolecular interactions in biology and materials science. Yet the types of interaction patterns that can be constructed using known coiled coils are limited. Here we greatly expand the coiled-coil toolkit by measuring t...
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American Chemical Society
2011
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Online Access: | http://hdl.handle.net/1721.1/67682 https://orcid.org/0000-0003-4074-8980 |
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author | Reinke, Aaron Wade Grant, Robert A. |
author2 | Massachusetts Institute of Technology. Department of Biology |
author_facet | Massachusetts Institute of Technology. Department of Biology Reinke, Aaron Wade Grant, Robert A. |
author_sort | Reinke, Aaron Wade |
collection | MIT |
description | The versatile coiled-coil protein motif is widely used to induce and control macromolecular interactions in biology and materials science. Yet the types of interaction patterns that can be constructed using known coiled coils are limited. Here we greatly expand the coiled-coil toolkit by measuring the complete pairwise interactions of 48 synthetic coiled coils and 7 human bZIP coiled coils using peptide microarrays. The resulting 55-member protein “interactome” includes 27 pairs of interacting peptides that preferentially heteroassociate. The 27 pairs can be used in combinations to assemble sets of 3 to 6 proteins that compose networks of varying topologies. Of special interest are heterospecific peptide pairs that participate in mutually orthogonal interactions. Such pairs provide the opportunity to dimerize two separate molecular systems without undesired crosstalk. Solution and structural characterization of two such sets of orthogonal heterodimers provide details of their interaction geometries. The orthogonal pair, along with the many other network motifs discovered in our screen, provide new capabilities for synthetic biology and other applications. |
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id | mit-1721.1/67682 |
institution | Massachusetts Institute of Technology |
language | en_US |
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publishDate | 2011 |
publisher | American Chemical Society |
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spelling | mit-1721.1/676822022-10-01T17:26:39Z A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering Reinke, Aaron Wade Grant, Robert A. Massachusetts Institute of Technology. Department of Biology Keating, Amy E. Keating, Amy E. Reinke, Aaron Wade Grant, Robert A. The versatile coiled-coil protein motif is widely used to induce and control macromolecular interactions in biology and materials science. Yet the types of interaction patterns that can be constructed using known coiled coils are limited. Here we greatly expand the coiled-coil toolkit by measuring the complete pairwise interactions of 48 synthetic coiled coils and 7 human bZIP coiled coils using peptide microarrays. The resulting 55-member protein “interactome” includes 27 pairs of interacting peptides that preferentially heteroassociate. The 27 pairs can be used in combinations to assemble sets of 3 to 6 proteins that compose networks of varying topologies. Of special interest are heterospecific peptide pairs that participate in mutually orthogonal interactions. Such pairs provide the opportunity to dimerize two separate molecular systems without undesired crosstalk. Solution and structural characterization of two such sets of orthogonal heterodimers provide details of their interaction geometries. The orthogonal pair, along with the many other network motifs discovered in our screen, provide new capabilities for synthetic biology and other applications. National Institutes of Health (U.S.) (NIH Award GM067681) National Institutes of Health (U.S.) (NCRR Award RR-15301) 2011-12-14T20:39:10Z 2011-12-14T20:39:10Z 2010-04 2009-09 Article http://purl.org/eprint/type/JournalArticle 0002-7863 1520-5126 http://hdl.handle.net/1721.1/67682 Reinke, Aaron W., Robert A. Grant and Amy E. Keating. "A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering." J. Am. Chem. Soc., 2010, 132 (17), pp 6025–6031. https://orcid.org/0000-0003-4074-8980 en_US http://dx.doi.org/10.1021/ja907617a Journal of the American Chemical Society Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Chemical Society Prof. Amy Keating |
spellingShingle | Reinke, Aaron Wade Grant, Robert A. A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering |
title | A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering |
title_full | A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering |
title_fullStr | A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering |
title_full_unstemmed | A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering |
title_short | A Synthetic Coiled-Coil Interactome Provides Heterospecific Modules for Molecular Engineering |
title_sort | synthetic coiled coil interactome provides heterospecific modules for molecular engineering |
url | http://hdl.handle.net/1721.1/67682 https://orcid.org/0000-0003-4074-8980 |
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