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...

Full description

Bibliographic Details
Main Authors: Reinke, Aaron Wade, Grant, Robert A.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: American Chemical Society 2011
Online Access:http://hdl.handle.net/1721.1/67682
https://orcid.org/0000-0003-4074-8980
_version_ 1826207467697078272
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.
first_indexed 2024-09-23T13:50:26Z
format Article
id mit-1721.1/67682
institution Massachusetts Institute of Technology
language en_US
last_indexed 2024-09-23T13:50:26Z
publishDate 2011
publisher American Chemical Society
record_format dspace
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
work_keys_str_mv AT reinkeaaronwade asyntheticcoiledcoilinteractomeprovidesheterospecificmodulesformolecularengineering
AT grantroberta asyntheticcoiledcoilinteractomeprovidesheterospecificmodulesformolecularengineering
AT reinkeaaronwade syntheticcoiledcoilinteractomeprovidesheterospecificmodulesformolecularengineering
AT grantroberta syntheticcoiledcoilinteractomeprovidesheterospecificmodulesformolecularengineering