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.
