Format

Send to

Choose Destination
Nat Chem Biol. 2013 Jun;9(6):362-6. doi: 10.1038/nchembio.1248. Epub 2013 Apr 28.

Design of a single-chain polypeptide tetrahedron assembled from coiled-coil segments.

Author information

1
Department of Biotechnology, National Institute of Chemistry, Ljubljana, Slovenia.

Abstract

Protein structures evolved through a complex interplay of cooperative interactions, and it is still very challenging to design new protein folds de novo. Here we present a strategy to design self-assembling polypeptide nanostructured polyhedra based on modularization using orthogonal dimerizing segments. We designed and experimentally demonstrated the formation of the tetrahedron that self-assembles from a single polypeptide chain comprising 12 concatenated coiled coil-forming segments separated by flexible peptide hinges. The path of the polypeptide chain is guided by a defined order of segments that traverse each of the six edges of the tetrahedron exactly twice, forming coiled-coil dimers with their corresponding partners. The coincidence of the polypeptide termini in the same vertex is demonstrated by reconstituting a split fluorescent protein in the polypeptide with the correct tetrahedral topology. Polypeptides with a deleted or scrambled segment order fail to self-assemble correctly. This design platform provides a foundation for constructing new topological polypeptide folds based on the set of orthogonal interacting polypeptide segments.

Comment in

PMID:
23624438
PMCID:
PMC3661711
DOI:
10.1038/nchembio.1248
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center